Duy Chi Trinh

Laurent Laplaze

Soazig Guyomarc

Lateral root formation: building a meristem de novo

Keywords: lateral root, root branching, root meristem formation, Arabidopsis, auxin, organogenesis, stem cell niche

The complex and adaptable architecture of the plant root system in soil is of paramount importance for crop growth and performance. Root growth depends on the activity of the root apical meristem, an organized population of proliferating progenitor cells continuously replenished from a stem cell niche. Root branching, which greatly contributes to root system architecture in most dicot species, consists in de novo formation of new root meristems in existing root tissues. This phenomenon illustrates the ability of plants to repeatedly generate new tissues specialized in post-embryonic continuous growth and greatly impacts the elaboration of the root system architecture and its adaptation to environmental constraints. Here, we review the recent findings and models related to lateral root organogenesis in the dicot species Arabidopsis 2 thaliana, with emphasis on the mechanisms controlling de novo root meristem formation.

Experimental evidence suggests that critical regulatory modules are common between embryonic and post-embryonic root meristem organogenesis, and that the lateral root formation molecular pathway is in part common with organ regeneration from callus.

Introduction

The root system fulfils multiple essential roles for the plant, including soil exploration and water and nutrient uptake, interactions with surrounding biotic and abiotic environments, plant anchorage to the substrate, and in some instances, vegetative reproduction or storage of photosynthates [START_REF] Beeckman | Annual Plant Reviews, Root Development[END_REF]. In doing so, it greatly influences crop performance and yield [START_REF] Rogers | Regulation of plant root system architecture: Implications for crop advancement[END_REF]. For example, changes in root system and water uptake explain a large part of the continuous increase in maize yield in the U.S. over the past 70 years [START_REF] Hammer | Can changes in canopy and/or root system architecture explain historical maize yield trends in the U.S. corn belt?[END_REF]. Root system architecture (RSA), which refers to the spatial configuration of the whole root system of a plant in soil, is a potent parameter influencing root system function and crop growth [START_REF] Lynch | Root Architecture and Plant Productivity[END_REF][START_REF] Lynch | TURNER REVIEW No. 14. Roots of the Second Green Revolution[END_REF][START_REF] Dorlodot | Root system architecture: opportunities and constraints for genetic improvement of crops[END_REF][START_REF] Rogers | Regulation of plant root system architecture: Implications for crop advancement[END_REF]. RSA traits have been frequently overlooked in past breeding programs due to the difficulty to access and quantify them. However, recent advances in phenotyping technologies and physiological modelling open the way for smart crop breeding programs targeting root traits and especially RSA [START_REF] Smith | Root system architecture: insights from Arabidopsis and cereal crops[END_REF][START_REF] Kuijken | Root phenotyping: From component trait in the lab to breeding[END_REF]. These new breeding strategies offer a valuable approach to meet the demand in crop production in the current challenging context of increasing global human population and intensifying adversary soil and climatic conditions [START_REF] Godfray | Food Security: The Challenge of Feeding 9 Billion People[END_REF][START_REF] Smith | Root system architecture: insights from Arabidopsis and cereal crops[END_REF]Tai et al., 2014).

Plant RSA is modulated by 1) root growth, i.e. increase in root length, 2) root angle and 3) root branching, i.e. the formation of new roots such as lateral roots (LRs, originating from existing roots including lateral roots) and adventitious roots (emerging from shoot tissues, such as stem bases; [START_REF] Osmont | Hidden Branches: Developments in Root System Architecture[END_REF][START_REF] Bellini | Adventitious roots and lateral roots: similarities and differences[END_REF]. Root growth relies on the activity of specialized tissues called root apical meristems that are organized populations of dividing cells including a self-maintained stem cell niche [START_REF] Aichinger | Plant stem cell niches[END_REF][START_REF] Choe | Push-pull strategy in the regulation of postembryonic root development[END_REF]; Figure 1). Secondary root formation consists of de novo organogenesis of new root meristems from seemingly differentiated tissues. Contribution of post-embryonic root organogenesis to the elaboration of the plant RSA varies greatly depending on the species. While the primary root and LRs emerging from it contribute to a significant extent to RSA development in dicot species, adventitious roots are predominant in RSA of most monocot species [START_REF] Bellini | Adventitious roots and lateral roots: similarities and differences[END_REF]. Root growth and branching are influenced by endogenous physiological cues as well as by environmental factors, such as soil texture, nutrient and water availability, and microbial interactions [START_REF] Malamy | Intrinsic and environmental response pathways that regulate root system architecture[END_REF][START_REF] Bao | Plant roots use a patterning mechanism to position lateral root branches toward available water[END_REF]Tian et al., 2014b;[START_REF] Morris | Shaping 3D Root System Architecture[END_REF]. This plasticity in RSA is of paramount importance for plant adaptation to environmental constraints. <Figure 1 near here> Meristems are complex tissues that consist of cells with little differentiation and that retain mitotic activity [START_REF] Aichinger | Plant stem cell niches[END_REF]. Division and differentiation of these cells are tightly regulated through a network of genetic factors and cell-to-cell communications providing plants with the ability to continuously generate new tissues and organs after germination. As a result, meristematic cells express repertoires of cell cycle-related genes but also specific factors influencing cell fate, such as chromatin modifiers and hormone and peptide signalling pathways (reviewed in Lee et al., 2013;[START_REF] Chiatante | Regulatory networks controlling the development of the root system and the formation of lateral roots: a comparative analysis of the roles of pericycle and vascular cambium[END_REF]. Regulators of the structural properties of the tissue such as cytoskeleton organization, cell membrane dynamics, as well as primary cell wall formation are also of great importance for meristematic activity [START_REF] Sassi | When biochemistry meets mechanics: A systems view of growth control in plants[END_REF].

Importantly, emergent properties in this intricate regulation network generate long-lasting dynamic organization at the tissue scale, and especially, the maintenance of a central stem cell niche. Stem cells are undifferentiated cells able to divide with no apparent limit, renewing the stem cell pool as well as producing progenitor cells that will participate in the production of one or more differentiated cell types [START_REF] Spradling | Stem cells find their niche[END_REF][START_REF] Laux | The stem cell concept in plants: A matter of debate[END_REF]. In plant meristems, stem cells are prevented from differentiating through signalling from another group of cells, the meristem organizing centre [START_REF] Doerner | Root development: quiescent center not so mute after all[END_REF]. Specifically in root apical meristems, the stem cells are called "initials" and the organizing centre is termed "quiescent centre" (QC; [START_REF] Choe | Push-pull strategy in the regulation of postembryonic root development[END_REF]. As in animal stem cell niches [START_REF] Fortunel | Comment on " 'Stemness': Transcriptional Profiling of Embryonic and Adult Stem Cells" and "A Stem Cell Molecular Signature[END_REF][START_REF] Zipori | The nature of stem cells: State rather than entity[END_REF], the transcriptomic signature of plant stem cells remains elusive, although association of some specific transcription factors has been shown to be important [START_REF] Galinha | PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development[END_REF][START_REF] Sarkar | Conserved factors regulate signalling in Arabidopsis thaliana shoot and root stem cell organizers[END_REF][START_REF] Scheres | Stem-cell niches: Nursery rhymes across kingdoms[END_REF][START_REF] Balaguer | Predicting gene regulatory networks by combining spatial and temporal gene expression data in Arabidopsis root stem cells[END_REF]. However, hormonal, epigenetic, and transcriptional regulators have been identified that play a critical role in stem cell niche establishment, organization, and maintenance [START_REF] Choe | Push-pull strategy in the regulation of postembryonic root development[END_REF]. Not surprisingly, some factors, such as cell cycle effectors, are important for both shoot and root meristems. In addition, common schemes involving related molecules participate in both shoot and root meristem organization. For example, the ratio between auxin and cytokinin hormonal signalling greatly influences the balance between cell division and differentiation, although with seemingly different outputs in shoot and root contexts [START_REF] Galinha | Hormonal input in plant meristems: A balancing act[END_REF]Vanstraelen & Benková, 2012). Additionally, in both shoot and root meristems transcription factors specifically expressed in the organizing centre inhibit the differentiation of neighbouring stem cells and are targets of a negative feedback mediated by non-cell autonomous peptides and membrane-located receptors [START_REF] Stahl | Moderation of arabidopsis root stemness dynamic input into robust patterning at the shoot apex[END_REF]. Nevertheless, other aspects of meristem regulation, and especially hormonal and peptide signal transduction and its impact on cell differentiation, are specific to root or shoot development [START_REF] Galinha | PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development[END_REF].

The root apical meristem activity continuously generates new cells that participate to root growth as well as to renewal of the root cap, an important interface of the root meristem with the environment [START_REF] Perilli | Growth and development of the root apical meristem[END_REF][START_REF] Petricka | Control of Arabidopsis Root Development[END_REF][START_REF] Sozzani | Postembryonic control of root meristem growth and development[END_REF]. Still, only one or few root apical meristems are generated during plant embryogenesis. A significant proportion of the root system of a growing plant thus originates from post-embryonic root formation through a tightly regulated sequence of cell division and differentiation. This organogenesis process implies precise changes in cell cycle activities as well as modifications in cell gene expression programs [START_REF] Birnbaum | How many ways are there to make a root?[END_REF].

This review focuses on lateral root (LR) development, i.e. root organogenesis from existing root tissues, with emphasis on the processes generating a new functional root meristem. To that purpose, we will predominantly consider the model plant Arabidopsis thaliana, in which LR formation has been extensively studied. Arabidopsis is a dicot plant whose RSA consists of a primary root, LRs of multiple orders, e.g. tertiary roots, and few adventitious roots [START_REF] Gutierrez | Auxin Controls Arabidopsis Adventitious Root Initiation by Regulating Jasmonic Acid Homeostasis[END_REF][START_REF] Smith | Root system architecture: insights from Arabidopsis and cereal crops[END_REF]. Arabidopsis primary roots and LRs have a relatively simple anatomy, making them a valuable model for developmental biology studies [START_REF] Lavenus | The Dicot Root as a Model System for Studying Organogenesis[END_REF]. The young Arabidopsis root is made of one layer of each tissue namely from the outside to the inside, the epidermis, the cortex, the endodermis and the pericycle enclosing the vascular tissues, which includes two xylem and two phloem poles [START_REF] Dolan | Cellular organisation of the Arabidopsis thaliana root[END_REF]; Figure 1). In addition, Arabidopsis is amenable to LR induction protocols, live imaging techniques, and genetic reporter and mutant strategies [START_REF] Koornneef | The development of Arabidopsis as a model plant[END_REF][START_REF] Jansen | Inducible System for Lateral Roots in Arabidopsis thaliana and Maize BT -Plant Organogenesis: Methods and Protocols[END_REF]. A wealth of information has been gathered on the processes regulating embryonic root meristem establishment, primary root meristem maintenance and plasticity, as well as on the cellular and molecular events underlying post-embryogenesis LR formation. Here, we synthesize recent published data highlighting observed properties of post-embryonic root meristem formation and aim to identify remaining gaps in our understanding of this biological process that greatly contributes to plant development and crop production.

Tissue context and early events of lateral root primordium organogenesis

Competence of pericycle cells for root organogenesis

LR formation in Arabidopsis originates exclusively from pericycle cells (Figure 2). The pericycle is a single layer of cells representing the outermost cells of the vascular cylinder (Beeckman & De Smet, 2014). Pericycle cells are produced by inner initials of the primary root meristem. Due to this anatomical position, some pericycle cells neighbour either xylem pole or phloem pole cells. Interestingly this relative positioning is of functional importance, since lateral root primordia (LRPs) originate exclusively from xylem-pole pericycle (XPP) cells in many plants such as Arabidopsis [START_REF] Dubrovsky | Pericycle cell proliferation and lateral root initiation in Arabidopsis[END_REF][START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF], and only from phloem pole pericycle cells in others such as maize [START_REF] Jansen | Phloem-associated auxin response maxima determine radial positioning of lateral roots in maize[END_REF]. <Figure 2 near here> What makes those pericycle cells competent for LRP initiation is not clearly understood.

However, a transcriptomic analysis in maize showed that compared to non-pericycle cells, pericycle cells preferentially express a subset of genes related to protein synthesis, transcription, and signal transduction, which could explain their competence for cell division [START_REF] Dembinsky | Transcriptomic and Proteomic Analyses of Pericycle Cells of the Maize Primary Root[END_REF]. In addition, analyses of the expression pattern of cell cycle regulators in roots suggested that stele tissues, including pericycle, retained S-phase related gene expression longer that other root tissues [START_REF] Beeckman | The peri-cell-cycle in Arabidopsis[END_REF]. Consistent with this hypothesis, a recent analysis of mitosis distribution in Arabidopsis root tips showed that, together with endodermis and vascular cells, pericycle cells retained mitotic activity longer than cortex cells or epidermis cells [START_REF] Lavrekha | 3D analysis of mitosis distribution highlights the longitudinal zonation and diarch symmetry in proliferation activity of the Arabidopsis thaliana root meristem[END_REF]. The pericycle actually consists of a heterogeneous population of cells: Arabidopsis XPP cells in the mature root retain some meristematic cell-specific features such as fragmented vacuoles, large nuclei and dense cytoplasm, and expression of S-phase related cell cycle regulators in contrast to "differentiated" pericycle cells [START_REF] Beeckman | The peri-cell-cycle in Arabidopsis[END_REF][START_REF] Casimiro | Dissecting Arabidopsis lateral root development[END_REF][START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF][START_REF] Almeida Engler | Systematic analysis of cellcycle gene expression during Arabidopsis development[END_REF] identified 16 cell cycle genes displaying preferential expression in the Arabidopsis XPP cell file. The D-type Cyclin CYCD4;1 gene is expressed in XPP cells in the root meristem, and its loss of function causes a premature elongation of these cells associated with a reduced LR density [START_REF] Nieuwland | The Dtype cyclin CYCD4;1 modulates lateral root density in Arabidopsis by affecting the basal meristem region[END_REF].

Conversely, phloem pole pericycle cells were shown to differentiate and become quiescent significantly earlier than other pericycle cells, including XPP cells [START_REF] Lavrekha | 3D analysis of mitosis distribution highlights the longitudinal zonation and diarch symmetry in proliferation activity of the Arabidopsis thaliana root meristem[END_REF].

Longer cell cycle activity in XPP cells exiting the root meristem is dependent on the activity of ABERRANT LATERAL ROOT FORMATION 4 (ALF4) as in the alf4 mutant XPP cells only weakly express the G2-to-M transition transgene CYCB1;1::GUS [START_REF] Celenza | A pathway for lateral root formation in Arabidopsis thaliana[END_REF][START_REF] Didonato | Arabidopsis ALF4 encodes a nuclearlocalized protein required for lateral root formation[END_REF]. ALF4 is widely expressed in plant tissues and encodes a plant-specific regulator modulating the activity of SCF complexes required for the signalling of the plant hormones auxin and gibberellin [START_REF] Bagchi | The Arabidopsis ALF4 protein is a regulator of SCF E3 ligases[END_REF]. Consistent with this longer cell cycle activity of pericycle cells being instrumental for LR formation, the alf4 mutant plants display a strong reduction in root branching, even in presence of the root-formation promoting hormone auxin [START_REF] Didonato | Arabidopsis ALF4 encodes a nuclearlocalized protein required for lateral root formation[END_REF][START_REF] Bagchi | The Arabidopsis ALF4 protein is a regulator of SCF E3 ligases[END_REF].

Importantly, XPP cells express specific repertoires of genes as exemplified by the J0121 enhancer trap line that displays robust GFP expression in XPP cell files from the elongation zone of the meristem onwards, as well as, interestingly, in related shoot tissues competent for root formation [START_REF] Casimiro | Auxin transport promotes Arabidopsis lateral root initiation[END_REF][START_REF] Laplaze | GAL4-GFP enhancer trap lines for genetic manipulation of lateral root development in Arabidopsis thaliana[END_REF]Sugimoto et al., 2010). Another enhancer trap line, Rm1007, showed GFP expression specifically in XPP cells and in the corresponding initials, adjacent to the root meristem QC, including in young embryos, indicating that the genomic region highlighted by the Rm1007 insertion drives very early XPP cell fate-specific expression [START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF].

The close relationship between vascular pole differentiation and pericycle cell competence for LR formation suggests a robust crosstalk between these two cell populations in the primary root meristem. For example, the Arabidopsis lonesome highway (lhw) mutant, that has only one xylem and one phloem pole, specifically produces LRP along that single xylem strand [START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF]. Conversely, roots of the wooden leg (wol) mutant lack phloem specification and the J0121 marker is present throughout the pericycle. Interestingly, despite this characteristic, LR formation is severely affected in the wol mutant background, suggesting that both xylem and phloem specification in the primary root is required for functional LR formation [START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF]. Patterning of xylem and phloem vascular identities in the central domain of the root meristem is regulated through a complex network of transcriptional signalling and hormonal crosstalk (reviewed in Vaughan-Hirsch et al., 2018). A combination of experimental and modelling approaches suggested that mutual inhibition between auxin and cytokinin signalling patterned the alternating of xylem and phloem poles in the Arabidopsis root meristem (Bishopp et al., 2011a). Signalling between vasculature identity and competence of pericycle cells for LR formation could involve auxin maxima in the xylem axis and phloem axis, in Arabidopsis and in maize, respectively [START_REF] Jansen | Phloem-associated auxin response maxima determine radial positioning of lateral roots in maize[END_REF][START_REF] El-Showk | Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, while Cytokinin Levels Out[END_REF]. Indeed, treatments by exogenous auxins or auxin transport inhibition alter the anatomical distinction between XPP and non XPP cells in Arabidopsis [START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF]. However, neither auxin nor cytokinin short term treatments modify the expression pattern of J0121 and Rm1007 transgenes, indicating a robust patterning mechanism of XPP cell identity in the root meristem [START_REF] Parizot | Diarch Symmetry of the Vascular Bundle in Arabidopsis Root Encompasses the Pericycle and Is Reflected in Distich Lateral Root Initiation[END_REF].

Oscillatory LR priming by endogenous cues

In Arabidopsis LRs originate only from XPP cells, but not every XPP cell develops into a LRP. Indeed in the basal meristem of the parental root tip, oscillating mechanisms periodically select subsets of XPP cells and prepare them to enter LR formation, a phenomenon called "priming" [START_REF] Möller | Dynamic control of lateral root positioning[END_REF]. This selection process has a major impact on RSA by defining the potential sites for root branching. The molecular processes underlying this priming event are still not fully understood, but are associated with changes in auxin signalling [START_REF] Smet | Auxin-dependent regulation of lateral root positioning in the basal meristem of Arabidopsis[END_REF].

Monitoring expression of the synthetic auxin-responsive DR5 (DIRECT REPEAT5) promoter revealed regular pulses of auxin signalling activity in the two protoxylem strands in the basal meristem. Transcriptomic analyses showed that the expression levels of hundreds of genes were also oscillating in that segment of the root, according to the same period as auxin signal oscillations [START_REF] Moreno-Risueno | Oscillating gene expression determines competence for periodic Arabidopsis root branching[END_REF]. While cells exit the basal meristem, those temporal fluctuations progressively cease and high signal stabilizes into local auxin maxima correlating with future sites of LR formation [START_REF] Smet | Auxin-dependent regulation of lateral root positioning in the basal meristem of Arabidopsis[END_REF][START_REF] Xuan | Root cap-derived auxin pre-patterns the longitudinal axis of the arabidopsis root[END_REF]. The specification of these sites with high and stable DR5 signal, termed prebranch sites, is dependent on auxin signal transduction and probably on a complex network of transcription factors [START_REF] Moreno-Risueno | Oscillating gene expression determines competence for periodic Arabidopsis root branching[END_REF]. The root cap plays a crucial role in creating these auxin pulses. First, a defect in auxin synthesis in the root cap impairs the amplitude of auxin signalling oscillations in the basal meristem, suggesting that auxin molecules that signal XPP priming may originate from the root cap [START_REF] Xuan | Root cap-derived auxin pre-patterns the longitudinal axis of the arabidopsis root[END_REF]. Second, periodic programmed cell death occurs in lateral root cap cells creating rhythmic influxes of auxin into inner cells of the elongation zone of the meristem, which tightly correlate with prebranch site formation [START_REF] Xuan | Cyclic programmed cell death stimulates hormone signaling and root development in Arabidopsis[END_REF]. Pulsating fluxes of auxin from the root cap to the meristem might participate in generating peaks in auxin signalling activity in the protoxylem cell files, contributing to prebranch site specification.

Basipetal (from the root tip shootward) auxin fluxes from the columella through the lateral root cap and the root epidermis have been extensively studied in Arabidopsis in particular in relation to gravitropism [START_REF] Rashotte | Basipetal Auxin Transport Is Required for Gravitropism in Roots of Arabidopsis[END_REF][START_REF] Wisniewska | Polar PIN localization directs auxin flow in plants[END_REF][START_REF] Band | Root gravitropism is regulated by a transient lateral auxin gradient controlled by a tipping-point mechanism[END_REF]. Consistent with the model of root cap-derived auxin priming XPP cells, parental root waving, mechanical bending, or gravistimulation modulate LR formation, possibly because of gravity-modulated auxin fluxes or changes in auxin routes due to tissue bending that affects shootward auxin distribution [START_REF] Ditengou | Mechanical induction of lateral root initiation in Arabidopsis thaliana[END_REF][START_REF] Laskowski | Root system architecture from 52 coupling cell shape to auxin transport[END_REF][START_REF] Lucas | An auxin transportbased model of root branching in Arabidopsis thaliana[END_REF][START_REF] Scheres | Root patterning: it takes two to tangle[END_REF]. However, even agar-constrained roots, growing with only little deviation from gravity, display oscillation in auxin signalling and regularly spaced prebranched sites [START_REF] Moreno-Risueno | Oscillating gene expression determines competence for periodic Arabidopsis root branching[END_REF]. This suggests that an endogenous clock mechanism produces uniformly spaced pre-branch sites to recruit pericycle cells and make them competent for de novo organogenesis.

Recently, Laskowski and ten Tusscher (2017) analysed the properties of the priming process in order to elucidate the molecular steps controlling auxin signalling oscillations and subsequent stabilization of auxin signal maximum. Both could rely on emergent properties (i.e. properties that arise from the collaborative functioning of a system, but do not belong to any one part of that system) of the global genetic system controlling auxin distribution, auxin signal transduction, and cell fate specification in the meristem [START_REF] Alon | Network motifs: Theory and experimental approaches[END_REF]. Feedback mechanisms can generate oscillating gene expression patterns that result in locally fluctuating transcriptomes [START_REF] Caluwé | A Compact Model for the Complex Plant Circadian Clock[END_REF] or, when combined with cell-to-cell communication, create spatial patterning of distinct cell identities (reviewed in [START_REF] Green | Positional information and reaction-diffusion: two big ideas in developmental biology combine[END_REF]. Other network motifs, i.e. specific association of gene regulatory interactions, can instead buffer variations in gene expression (e.g. Vernoux et al., 2011). Particularly interesting in a developmental perspective are regulatory network properties that make the system "choose" between two potential dynamic trends, causing bifurcation in system state trajectories, distinct cell fates and potentially symmetry breaking at a tissue scale (Bishopp et al., 2011a). Such critical properties are described in various aspects of plant developmental regulation by auxin, including in root tissues.

Feedback of cell parameters on auxin transporter expression and polarization can create and enhance non-uniform auxin distribution across tissues in a robust manner. As a result, asymmetric auxin distribution, locally transduced by cell specific signalling mechanisms, can create shifts in cell identity among neighbours. [START_REF] Norman | To branch or not to branch: the role of pre-patterning in lateral root formation[END_REF] propose that the priming process, caused by auxin signal pulses, could enhance cell sensitivity to later auxin accumulation and its competence to translate it into the onset of a new organogenesis program.

Bistable properties of auxin signalling modules could explain the "memorization" of that auxin signal in the prebranch sites only. Such a toggle-switch behaviour of an auxin-signalling motif has been described [START_REF] Lau | Auxin triggers a genetic switch[END_REF].

Lateral root founder cell specification

Within some prebranch sites, a subset of pericycle cells is later specified to become lateral root founder cells. Founder cells (FCs) refer to pre-existing cells that initiate the formation of a new organ through cell division [START_REF] Laskowski | Formation of lateral root meristems is a two-stage process[END_REF]; thus FC specification corresponds to the last apparent transition in cell identity before the onset of organogenesis. FC specification again involves a local increase in auxin signalling [START_REF] Smet | Auxin-dependent regulation of lateral root positioning in the basal meristem of Arabidopsis[END_REF][START_REF] Rybel | A novel Aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity[END_REF][START_REF] Moreno-Risueno | Oscillating gene expression determines competence for periodic Arabidopsis root branching[END_REF][START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF]. Selective stimulation of auxin production in one or several pericycle cells is sufficient to transform them into FCs and trigger LR organogenesis [START_REF] Dubrovsky | Auxin acts as a local morphogenetic trigger to specify lateral root founder cells[END_REF]. Conversely, in normal conditions, emergent properties of the auxin transport and signalling network may explain why, while XPP cell specification, priming and prebranch site definition may occur symmetrically on both xylem poles of the Arabidopsis vascular cylinder [START_REF] Smet | Auxin-dependent regulation of lateral root positioning in the basal meristem of Arabidopsis[END_REF][START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF], effective initiation of LR development only occurs on one of those two sides [START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF][START_REF] El-Showk | Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, while Cytokinin Levels Out[END_REF].

Auxin transcriptomic signalling is known to involve degradation of Aux/IAA proteins and activation of associated AUXIN RESPONSE FACTOR (ARF)-family transcription factors (reviewed in [START_REF] Weijers | Transcriptional Responses to the Auxin Hormone[END_REF]. Interestingly, an auxin signalling pathway involving IAA28 and several ARFs it interacts with is required for FC specification [START_REF] Rybel | A novel Aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity[END_REF]. This auxin signalling module induces the expression of the transcription factor GATA23 in pericycle cells that will develop into a LRP before any sign of LR initiation (Figure 2).

Artificially inducing GATA23 expression in the pericycle greatly increases LRP density, indicating that it positively regulates LR formation [START_REF] Rybel | A novel Aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity[END_REF]. GATA23 is therefore considered a marker for LR FCs, but its targets relevant for LR formation remain unknown.

Interestingly, GATA23 expression is also positively controlled by RAPID ALKALINIZATION FACTOR 34 (RALFL34), a small signalling peptide that could participate in auxin-mediated regulation of FC specification [START_REF] Murphy | RALFL34 regulates formative cell divisions in Arabidopsis pericycle during lateral root initiation[END_REF].

Chromatin remodelling factors, for example Polycomb group (PcG) proteins, are known to regulate developmental transitions in both plants and animals by modulating the expression of key developmental genes [START_REF] Schuettengruber | Genome Regulation by Polycomb and Trithorax: 70 Years and Counting[END_REF]. PcG proteins can form two multiprotein complexes: Polycomb repressive complex 1 (PRC1) and PRC2 which modify histone marks on chromatin to repress gene expression [START_REF] Derkacheva | Variations on a theme: Polycomb group proteins in plants[END_REF]. Arabidopsis mutants impaired in subunits of the PRC2 complex CURLY LEAF (CLF) and EMBRYONIC FLOWER basal meristem and in presumptive FCs, and directly represses the expression of the auxin efflux carrier-encoding gene PIN-FORMED 1 (PIN1) via histone modification [START_REF] Gu | A Histone H3 Lysine-27 Methyltransferase Complex Represses Lateral Root Formation in Arabidopsis thaliana[END_REF]. PIN-FORMED 1 participates to auxin signal concentration in the root tip and in LRPs [START_REF] Benková | Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation[END_REF][START_REF] Blilou | The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots[END_REF]. Accordingly, an increase in the auxin-sensitive DR5 promoter activity was reported in root apical meristems and in FCs of a loss-of-function clf mutant [START_REF] Gu | A Histone H3 Lysine-27 Methyltransferase Complex Represses Lateral Root Formation in Arabidopsis thaliana[END_REF]. Other chromatin remodelling processes were shown to participate in the regulation of cell fate transition during LR founder cell specification, such as histone deacetylation [START_REF] Singh | SWP1 negatively regulates lateral root initiation and elongation in Arabidopsis[END_REF], ATP-dependent chromatin remodelling [START_REF] Fukaki | PICKLE is required for SOLITARY-ROOT/IAA14-mediated repression of ARF7 and ARF19 activity during Arabidopsis lateral root initiation[END_REF][START_REF] Ho | PICKLE is a CHD subfamily II ATPdependent chromatin remodeling factor[END_REF], or histone variant deposition [START_REF] Manzano | Auxin and Epigenetic Regulation of SKP2B, an F-Box That Represses Lateral Root Formation[END_REF]. The precise hierarchy of these regulatory levels in combination with the auxin signalling network remains to be elucidated. Plasma membrane-located signalling processes during FC specification are suggested by the impaired conversion of prebranch sites into LRP in a mutant defective in the MEMBRANE-ASSOCIATED KINASE REGULATOR4 (MAKR4) gene [START_REF] Xuan | Root cap-derived auxin pre-patterns the longitudinal axis of the arabidopsis root[END_REF]. The MAKR4 protein belongs to the same protein family as MAKR5 [START_REF] Kang | Arabidopsis MAKR5 is a positive effector of BAM3-dependent CLE45 signaling[END_REF] and BRI1 KINASE INHIBITOR 1 (BKI1; [START_REF] Wang | Brassinoteroids regulate dissociation of BKI1, a negative regulator of BRI1 signaling, from the plasma membrane[END_REF][START_REF] Jiang | The Intrinsically Disordered Protein BKI1 Is Essential for Inhibiting BRI1 Signaling in Plants[END_REF], that are regulators of receptor kinases-associated signalling pathways. Expression of MAKR4, which is induced by auxin, is strongly enhanced in pericycle cells before cell division occurs and displays oscillations similar to that of DR5::LUC reporter expression. Importantly, the makr4 mutant has a normal number of prebranch sites but produces fewer LRP, and overexpression of MAKR4 promotes LRP formation. The data indicates that MAKR4 participates in the transition of a prebranch site into a LRP [START_REF] Xuan | Root cap-derived auxin pre-patterns the longitudinal axis of the arabidopsis root[END_REF].

Proper cell-to-cell communication via plasmodesmata is also necessary for correct LR FC specification [START_REF] Benitez-Alfonso | Symplastic Intercellular Connectivity Regulates Lateral Root Patterning[END_REF]. In plasmodesmal-localized b-1,3-glucanase 1 (pdbg1), pdbg2 single and double mutants whose increased callose deposition in the stele and LRPs block plasmodesmata, LRs are formed at higher density, sometimes even fused to each other [START_REF] Benitez-Alfonso | Symplastic Intercellular Connectivity Regulates Lateral Root Patterning[END_REF]. Closer inspection revealed expanded domains of GATA23 expression and auxin signalling activity (as reported by DR5 promoter-based transgene expression) around FCs, indicating that the correct function of these plasmodesmata-located proteins is necessary to restrict FC specification to a subset of selected cells. How exactly symplastic communication keeps LR formation in check is currently not understood, but possibly through the movement of non-cell autonomous factors, such as transcription factors, peptides, metabolites or hormones (Bishopp et al., 2011b;[START_REF] Norman | Intercellular Communication during Plant Development[END_REF][START_REF] Benitez-Alfonso | Symplastic Intercellular Connectivity Regulates Lateral Root Patterning[END_REF][START_REF] Benitez-Alfonso | Symplastic intercellular transport from a developmental perspective[END_REF][START_REF] Yue | Cell-to-cell communication during lateral root development[END_REF].

Lateral root primordia initiation

In Arabidopsis, LRP initiation is first visually recognized by the swell of LR FCs, together with the shrink in volume of overlaying endodermal cells (Vermeer et al., 2014). Subsequently, nuclei of two longitudinally adjacent FCs, in each row, migrate to the common cell wall (De [START_REF] Rybel | A novel Aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity[END_REF]. Then these two cells undergo an anticlinal and asymmetric division yielding two shorter daughter cells next to each other [START_REF] Casimiro | Auxin transport promotes Arabidopsis lateral root initiation[END_REF][START_REF] Rybel | A novel Aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity[END_REF]. This typical cell division occurs in 4 to 6 abutting pericycle cell files concomitantly [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF]. Because this asymmetric cell division produces two daughter cells with distinct shape and fate, it is a formative rather than a proliferative cell division [START_REF] Gunning | Formative and proliferative cell divisions, cell differentiation, and developmental changes in the meristem of Azolla roots[END_REF][START_REF] Smolarkiewicz | Formative cell divisions: Principal determinants of plant morphogenesis[END_REF]. Occurring independently of an established stem cell niche context and in a seemingly differentiated tissue, it is a landmark of the initiation of a new developmental program [START_REF] Smet | Asymmetric cell division in land plants and algae: The driving force for differentiation[END_REF]. This first round of pericycle cell division produces the so-called stage I LRP [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]. LRP initiation can also occur in a less common way from files of single pericycle cells [START_REF] Dubrovsky | Early primordium morphogenesis during lateral root initiation in Arabidopsis thaliana[END_REF][START_REF] Smet | Lateral root initiation or the birth of a new meristem[END_REF].

The swelling of FCs prior the first asymmetric cell division is assisted by volume loss of endodermal cells induced by auxin perception (Vermeer et al., 2014). Indeed, when endodermal cells expressed the stabilized form of SHY2, an Aux/IAA auxin signalling inhibitor, they were unable to lose their volume, hence maintained their turgidity. In those conditions underlying pericycle cells could not swell nor initiate asymmetric cell division, indicating that this space accommodation interaction between pericycle and endodermis is necessary for LR initiation (Vermeer et al., 2014). Moreover, ablation of an overlying endodermal cell triggers pericycle cell division, although in a periclinal manner, unless auxin was added [START_REF] Marhavý | Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation[END_REF]).

An early characteristic feature of LR initiation is the change of cell polarity revealed by nuclear migration in pericycle cells preceding the asymmetric cell division. This is controlled by auxintriggered expression of the LATERAL ORGAN BOUNDARIES DOMAIN (LBD) family transcription factors LBD16, LBD18 and LBD33 in pericycle cells [START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF]. The expression of LBD16 in XPP and FCs is dependent on the SLR/IAA14-ARF7-ARF19 auxin signalling pathway [START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF]. Interestingly, artificially converting LBD16 into a transcriptional repressor does not affect auxin signal in LR FCs but blocks the polar nuclear migration and subsequent anticlinal division of these cells, suggesting that the SLR/IAA14-ARF7-ARF19-LBD16 signalling cascade transduces auxin signalling into changes in pericycle cell polarity [START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF]. The transcription factor bZIP59 physically interacts with LBDs, including LBD16, LBD17 and LBD29 to control LRP initiation [START_REF] Xu | Control of auxin-induced callus formation by bZIP59-LBD complex in Arabidopsis regeneration[END_REF].

Transcriptomic analysis of auxin-induced LR initiation shed light on the early molecular events leading to pericycle cell division (Vanneste et al., 2005;[START_REF] Smet | Receptor-Like Kinase ACR4 Restricts Formative Cell Divisions in the Arabidopsis Root[END_REF][START_REF] Almeida Engler | Systematic analysis of cellcycle gene expression during Arabidopsis development[END_REF]. Cell cycle progression is tightly regulated by an intricate and dynamic network involving transcription regulators (such as E2F and RBR) and cyclin-dependent kinases whose activity is post-transcriptionally regulated by phosphorylation, protein-protein interaction, as well as APC/C-mediated ubiquitination and degradation [START_REF] Komaki | Control of the plant cell cycle by developmental and environmental cues[END_REF][START_REF] Breuer | Endocycling in the path of plant development[END_REF][START_REF] Genschik | Selective protein degradation: A rheostat to modulate cell-cycle phase transitions[END_REF]. One G1-to-S phase specific gene (CYCD3;2), one S-specific gene (CYCA2;4) and two G2-to-M related genes (CYCB2;5 and CDKB2;1) are upregulated in roots submitted to auxin-induced LR formation (Vanneste et al., 2005). Conversely, some genes encoding cell cycle inhibitors such as KRP2, KRP4, KRP7 and WEE1 are downregulated in the pericycle upon auxin treatment [START_REF] Almeida Engler | Systematic analysis of cellcycle gene expression during Arabidopsis development[END_REF]. In normal conditions, the CYCB1;1 gene, encoding a G2-to-M transition specific cyclin, is strongly expressed in XPP cells undergoing the first division [START_REF] Beeckman | The peri-cell-cycle in Arabidopsis[END_REF][START_REF] Himanen | Auxin-Mediated Cell Cycle Activation during Early Lateral Root Initiation[END_REF].

In addition to the change in LR FC cell polarity, SLR/IAA14-dependent auxin signalling is essential for their first divisions. Either slr gain of function mutation or loss of function mutation of its two ARF partners ARF7 and ARF19 prevents LR formation because the first anticlinal and subsequent periclinal divisions of pericycle cells are blocked [START_REF] Fukaki | Lateral root formation is blocked by a gain-of-function mutation in the solitary-root/IAA14 gene of Arabidopsis[END_REF]. The implication of SLR/IAA14 in priming and FC specification can be excluded because it is not expressed in basal meristem [START_REF] Fukaki | Lateral root formation is blocked by a gain-of-function mutation in the solitary-root/IAA14 gene of Arabidopsis[END_REF] and competence for LR FC specification of slr pericycle cells is still maintained [START_REF] Smet | Auxin-dependent regulation of lateral root positioning in the basal meristem of Arabidopsis[END_REF][START_REF] Rybel | A novel Aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity[END_REF]. The transcriptomic analysis by Vanneste et al. (2005), demonstrated that specific G1-to-S, S, and G2to-M cell cycle regulators act downstream of IAA14-ARF7-ARF19 mediated auxin signalling. In addition, active ARF7 and ARF19 transcription factors stimulate the expression of LBD18 and LBD33 which in turn stimulate the expression of E2Fa, a potent activator of S-phase promoting gene expression [START_REF] Berckmans | Auxin-Dependent Cell Cycle Reactivation through Transcriptional Regulation of Arabidopsis E2Fa by Lateral Organ Boundary Proteins[END_REF]. Another pathway for auxin-mediated cell cycle reactivation in XPP cells could consist in the downregulation of KRP2, an inhibitor of CYCD2;1-CDKA complex activity which could stimulate G1-to-S transition [START_REF] Sanz | The Arabidopsis D-Type Cyclin CYCD2;1 and the Inhibitor ICK2/KRP2 Modulate Auxin-Induced Lateral Root Formation[END_REF].

The first asymmetric cell division in LRP formation is also regulated by a peptide belonging to the GOLVEN/root growth factor/CLE-like (GLV/RGF/CLEL) family, GLV6 [START_REF] Fernandez | The GLV6/RGF8/CLEL2 peptide regulates early pericycle divisions during lateral root initiation[END_REF]. GLV6 is expressed in FCs preceding the migration of nuclei, and GLV6 silencing or overexpressing lines display decreased or increased FC division, respectively. In addition, overexpression of GLV6 or treatment of roots with GLV6 peptides disrupts the migration of FC nuclei to the common cell wall without disturbing cell cycle progression, converting the asymmetric cell division into a symmetric division [START_REF] Fernandez | The GLV6/RGF8/CLEL2 peptide regulates early pericycle divisions during lateral root initiation[END_REF]. Thus cell-to-cell communication mediated by GLV6 and possibly other GLV/RGF/CLEL family peptides is probably involved in the correct coordination of the asymmetric LR FC division [START_REF] Fernandez | The GLV6/RGF8/CLEL2 peptide regulates early pericycle divisions during lateral root initiation[END_REF].

The double mutant impaired in AURORA kinases (aur1 aur2) shows a strong defect in division plane orientation during LR formation, as early as the first asymmetric cell division. Although LR initiation density and polar localization of FC nuclei are unaffected, the positioning of the new cell wall is uncontrolled ( [START_REF] Damme | Arabidopsis α Aurora Kinases Function in Formative Cell Division Plane Orientation[END_REF]. Interestingly, while this results in a reduced proportion of emerged LRPs, this does not totally preclude LR formation, indicating the robustness of this organogenesis program ( [START_REF] Damme | Arabidopsis α Aurora Kinases Function in Formative Cell Division Plane Orientation[END_REF].

Control of lateral root spacing/density

Mechanisms controlling LR FC specification and LRP initiation along the primary root deeply impact the overall root branch production, i.e. LRP density (number of LRPs divided by the length of the parent root). In addition, other factors are required for efficient LRP spacing. The gene encoding the membrane localized receptor-like kinase ARABIDOPSIS CRINKLY4 (ACR4) is expressed specifically in the short daughter cells after the first asymmetric cell division. The acr4 mutant produces LRPs at higher densities and these LRPs usually stretch, sometimes even fuse together, indicating that ACR4, and possibly related kinases, control cell proliferation and spacing of newly initiated LRPs (De [START_REF] Smet | Receptor-Like Kinase ACR4 Restricts Formative Cell Divisions in the Arabidopsis Root[END_REF]. ACR4 was proposed to be the receptor of GLV6 and other related peptides [START_REF] Fernandez | Transcriptional and Functional Classification of the GOLVEN/ROOT GROWTH FACTOR/CLE-Like Signaling Peptides Reveals Their Role in Lateral Root and Hair Formation[END_REF], and possibly to transduce perceived signals inside the cell through a phosphorylation cascade involving the PROTEIN PHOSPHATASE 2A (PP2A; [START_REF] Yue | PP2A-3 interacts with ACR4 and regulates formative cell division in the Arabidopsis root[END_REF]. Cytokinins synthesized at the flanks of existing LRP was found to act as an inhibitor of LRP initiation, thereby preventing closely formed LRPs [START_REF] Chang | Cytokinin as a positional cue regulating lateral root spacing in Arabidopsis[END_REF]. Interestingly, expression of ACR4 and GLVs were significantly reduced in mutants defective in cytokinin biosynthesis, but ACR4 and cytokinins seems to act in partially separate pathways [START_REF] Chang | Cytokinin as a positional cue regulating lateral root spacing in Arabidopsis[END_REF]. Another peptide, C-TERMINALLY ENCODED PEPTIDE 5 (CEP5), is also involved in the regulation of LRP initiation and positioning [START_REF] Roberts | CEP5 and XIP1/CEPR1 regulate lateral root initiation in Arabidopsis[END_REF]. Overexpression of the CEP5 gene and exogenous treatment by the CEP5 peptide reduce LRP initiation events and induce the formation of closely positioned LRs, while CEP5 RNAi lines display an increase in LRP stage I and II density. Remarkably, CEP5 is expressed specifically in phloem pole pericycle cells and adjacent phloem cells, indicating an unknown crosstalk between different pericycle populations [START_REF] Roberts | CEP5 and XIP1/CEPR1 regulate lateral root initiation in Arabidopsis[END_REF]. Similarly, the PLETHORA (PLT) transcription factors PLT3, PLT5, PLT7 act redundantly downstream of the ARF7-and ARF19-mediated auxin signalling pathway to regulate LRP spacing [START_REF] Hofhuis | Phyllotaxis and rhizotaxis in Arabidopsis are modified by three plethora transcription factors[END_REF].

20

In summary, cells competent for LR formation are pericycle cells that have been progressively selected through a series of regulatory events: competence acquisition (or conservation) in the root meristem along with vascular strands patterning; priming of subsets of these cells through an endogenous clock mechanism followed by memorization of the prebranch site status, and eventually initiation of the LR organogenesis program revealed by anticlinal asymmetric cell division of so-called LR FCs. At each of these steps, local auxin signalling is involved in cell selection and state transition. Regular LR patterning along the root results from a robust emergent behaviour of the endogenous regulatory system (Figure 2). Still, this system allows the integration of environmental inputs, which translate into changes in auxin distribution, thus allowing adaptive responses of LR initiation to environmental constraints [START_REF] Yu | Cell Type-Specific Gene Expression Analyses by RNA Sequencing Reveal Local High Nitrate-Triggered Lateral Root Initiation in Shoot-Borne Roots of Maize by Modulating Auxin-Related Cell Cycle Regulation[END_REF][START_REF] Yu | Root Type-Specific Reprogramming of Maize Pericycle Transcriptomes by Local High Nitrate Results in Disparate Lateral Root Branching Patterns[END_REF].

Building a new organ: a coherent program of coordinated cell divisions, with newly set axis of growth and boundaries

After initiation, LRPs evolve in terms of tissue organization and morphology, developing in a direction perpendicular to the main root axis. LRP development is categorized into stages characterized by structural and positional features [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]; Figure 3). Briefly, LRPs of stage I, II, III and IV are one, two, three and four cell layers thick, respectively, thanks to successive periclinal divisions. Stage V LRPs penetrate the endodermis and are characterized by two cuboidal cells of the second outermost layer. At stage VI, LRPs have the typical dome shape reminiscent of the primary root tip, and its outermost layer has around 12 cells. LRPs of stage VII are more complex structurally and touching the epidermis, ready for emergence [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]. From founder cells to an emerged LR, LRP organogenesis relies on a series of cell divisions in different planes that need to be well coordinated to ensure proper organization and development of the new organ. <Figure 3 near here>

Control and sequence of cell division and division planes

As mentioned above, cell division is instrumental in LRP organogenesis, and in Arabidopsis conserved landmarks define important steps in the process of new LR formation. However, in contrast to embryo organogenesis which follows a highly regular cell lineage [START_REF] Palovaara | Tissue and Organ Initiation in the Plant Embryo: A First Time for Everything[END_REF], cell division in developing LRPs do not follow a fully stereotypic sequence, leading to significant differences in cell numbers between LRPs of the same stage [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF][START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF]. Nevertheless, modelling and experimental observation revealed that division of LRP cells may follow a small set of rules: (i) cells tend to follow the "shortest wall" principle, meaning that the positioning and geometry of newly formed cell wall frequently minimize the surface contact between the two daughter cells, (ii) cells often alternate their division plane (i.e. periclinal and anticlinal) between two consecutive divisions, and (iii) the outer layer predominantly divides periclinally prior to the inner layer (von [START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF]. Remarkably, despite variation in cell number, LRP shapes at a particular stage appear to be consistent [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF], indicating some higher levels of regulation contributing to the dome shape formation. Differential contribution of each pericycle founder cell to the LRP organogenesis participates in this dome shape development. In live time course analysis, ~60% of the LRP cell population derived from two or five founder cells (von [START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF]. Importantly, mutants of AURORA kinases, that are impaired in the control of cell division planes, can still form LRPs having typical domed-shape but lacking layered organization ( [START_REF] Damme | Arabidopsis α Aurora Kinases Function in Formative Cell Division Plane Orientation[END_REF][START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF]. All the data points to a great conservation in shape formation of developing LRPs.

Changes in cell division planes guide major transitions during the LRP morphogenesis, namely, the establishment of a new axis of growth, perpendicular to the main axis of the parental root, and the transition from bilateral to radial development. The first transition corresponds to the first periclinal divisions of stage I primordium cells, creating two cell layers characteristic of the stage II primordium. What controls this perpendicular shift in cell division plane orientation is currently not clearly understood. A long-standing model for cell division plane orientation in plants, which can be formulated as the "shortest wall" rule, proposes that the new cell wall follows one of the possible configurations that minimize the interface area between the two daughter cells. This model fits observed cell division planes in many cases, especially in embryos, shoot meristems, and LR development [START_REF] Yoshida | Genetic control of plant development by overriding a geometric division rule[END_REF][START_REF] Louveaux | Cell division plane orientation based on tensile stress in Arabidopsis thaliana[END_REF][START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF]. However even in those contexts in some instances, this model could not predict division plane orientation. Monitoring of the first periclinal division in the developing LRP using light sheet microscopy showed that only 50% of the dividing cells followed the "shortest wall" rule (von [START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF]. More recently, a mechanical, tension-based rule for cell division plane orientation was proposed [START_REF] Louveaux | Cell division plane orientation based on tensile stress in Arabidopsis thaliana[END_REF]. This rule could explain cell division plane orientation better than the "shortest wall" principle in tissues submitted to anisotropic forces, which could be the case for the swelling pericycle cells constrained between the underlying XPP cells, the overlaying endodermis, and the neighbouring pericycle cells. Interestingly, endodermis cell ablation, which modifies mechanical constraints in the surrounding tissues, provokes the periclinal cell division of the underlying pericycle cell [START_REF] Marhavý | Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation[END_REF]. Alternatively, high auxin concentration was proposed to instruct dividing cells to escape the default "shortest wall" rule during embryo development [START_REF] Yoshida | Genetic control of plant development by overriding a geometric division rule[END_REF]. Dividing pericycle cells are known to be sites of high auxin signalling, dependent from convergent auxin transport from neighbouring pericycle cells as well as overlaying endodermal cells [START_REF] Benková | Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation[END_REF][START_REF] Marhavý | Auxin reflux between the endodermis and pericycle promotes lateral root initiation[END_REF]. Strikingly, auxin supplementation after endodermis cell ablation causes ectopic pericycle cell division plane to shift from periclinal to anticlinal [START_REF] Marhavý | Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation[END_REF]. Altogether, this data supports the hypothesis that auxin distribution across the tissue and/or mechanical constraints influence formative periclinal cell plane orientation and the onset of the LRP growth axis.

Interestingly, by meticulously documenting the orientation of cell division in 3D of hundreds LRPs from stage I to VI, [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF] found that cells on the flanks of LRPs undergo either tangential or radial division. As a consequence, these cells form a ring surrounding the mass of daughter cells originated from the central cell files, contributing to the transition from the bilateral structure of the newly initiated LRP to its radial structure at later stages [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF]. Because of the particular position of these cells at the flanks of the developing primordium, their specific division geometry could also be influenced by local mechanical or hormonal cues.

LRP cellular organization and anatomical patterning

During regular Arabidopsis LR development, the sequence of cell divisions, although not fully stereotyped, produce conserved anatomical landmarks in the elaboration of the LRP cellular patterning [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]. Notably, important transitions are (i) the first round of periclinal cell divisions at the stage I to II transition, (ii) the organisation of a small group of subapical cells reminiscent of a meristem-organizing centre at the stage IV to V transition, concomitant with LRP breaking through the endodermis, acquiring dome shape and radial symmetry [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF], and (iii) the elongation of basal cells during LRP emergence [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]; Figure 3). These transitions highlight changes in the identity and behaviour of some LRP cells and contribute to the LRP functional patterning. For instance, specific gene expression profiles distinguish the outer layer from the inner layer cells in stage II LRPs. The expression of SCARECROW (SCR) is first detected specifically in the outer layer of stage II LRP, while SHORT-ROOT (SHR) expression is detected weakly from stage I and in both inner and outer layers of stage II LRP [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]Tian et al., 2014a;[START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. Gene expression patterns become more and more complex as the LRP grows and organizes into a new root apical meristem. The molecular events controlling de novo meristem patterning will be addressed in the next section. First, we will consider major regulators of overall LRP morphogenesis and patterning.

Analysis of auxin signalling (as reported by DR5-based reporter expression) in developing primordia shows that while being strongly and homogenously enhanced in stage I LRP as compared to surrounding tissues, auxin activity is gradually confined to the central cells in outer cell layers of developing LRPs, and to the tip of emerged LRs [START_REF] Benková | Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation[END_REF]. In various tissues, gradients of auxin distribution are known to be predominantly controlled by the polar localization of PIN-FORMED family auxin carriers, although other auxin transporters, or auxin biosynthesis or degradation, can participate [START_REF] Petrasek | Auxin transport routes in plant development[END_REF][START_REF] Zhao | Auxin Biosynthesis and Its Role in Plant Development[END_REF]Tang et al., 2017). Several members of the PIN family are expressed in developing primordia, including PIN1 and PIN3, although for some genes experimental results differ depending on the reporter constructs used [START_REF] Benková | Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation[END_REF][START_REF] Guyomarc'h | Early development and gravitropic response of lateral roots in Arabidopsis thaliana[END_REF]. Notably the pPIN1::PIN1:GFP reporter construct (rescuing the pin1 mutant phenotype) is expressed early during LRP development and the recombinant protein displays a polar distribution in the cell membrane pointed to the primordium tip, consistent with DR5-reported auxin signalling gradients. LRPs produced in a context of impaired auxin transport, either through genetic mutations or chemical treatments, display dramatic alterations in shape and organization and eventually often fail to emerge [START_REF] Benková | Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation[END_REF][START_REF] Geldner | The Arabidopsis GNOM ARF-GEF mediates endosomal recycling, auxin transport, and auxin-dependent plant growth[END_REF][START_REF] Moriwaki | Hormonal Regulation of Lateral Root Development in Arabidopsis Modulated by MIZ1 and Requirement of GNOM Activity for MIZ1 Function[END_REF]. Conversely, artificially inducing pericycle cell division, either by cyclin transgenic expression or by endodermal cell ablation, provokes the accumulation of cells without any sign of primordium patterning unless auxin is added (Vanneste et al., 2005;[START_REF] Marhavý | Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation[END_REF]. This data collectively demonstrates that non-uniform auxin distribution in the primordium is instructive for its cellular organization.

The distribution pattern of PIN proteins is regulated by the PLT genes, a family of AINTEGUMENTA-like transcription factors which have multiple roles in auxin-regulated root development [START_REF] Blilou | The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots[END_REF][START_REF] Galinha | PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF][START_REF] Scheres | Coordination of growth in root and shoot apices by AIL/PLT transcription factors[END_REF]. While PLT3, PLT5 and PLT7 are expressed in some pericycle cells prior to the first asymmetric cell division of LRP, PLT1, PLT2 and PLT4 are expressed in LRP of later stages [START_REF] Hofhuis | Phyllotaxis and rhizotaxis in Arabidopsis are modified by three plethora transcription factors[END_REF]. The expression of PLT3, PLT5 and PLT7 is required for the expression of PLT1, PLT2 and PLT4, so that the triple mutant plt3 plt5 plt7 is actually a PLT null mutant in the context of LRP development [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. A majority of LRP in the triple mutant plt3 plt5 plt7 lack periclinal cell division in early stages and show abnormal cell division planes at later stages, resulting in abnormally shaped LRPs. These LRPs have very low expression of PINs including PIN1 and PIN3. Very few LRPs of this mutant are able to emerge [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF], again pointing to the role of polar auxin distribution in LRP development. Some transcription factors were shown to play a critical role during the first step of LRP cellular organization. The GRAS family transcription factor SHORTROOT (SHR) gene is expressed in primary meristem stele, including the pericycle and stage I developing LRP, and the SHR protein is also detected in the overlying endodermis layer [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. As early as stage II, the cytoplasmic SHR protein is confined to the inner layer or the developing LRP, while nuclear SHR proteins are detected in the outer cell layer [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. Concomitantly expression of an SHR target, the related transcription factor SCR gene, is initiated in the outer layer of stage II primordia, and later is restricted to the second outermost layer, contacting the SHR-expression domain [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. Importantly, analysis of loss-of-function mutants showed that SHR function is required for proper lateral LRP organization (Lucas et al., 2011a;[START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF].

In addition, SCR controls specifically the cell division in the outer layer of stage II primordia. In scr-3 mutant primordia, this division is blocked whereas cell division in the inner layer continues with little modifications compared to the wild type. As a consequence, the scr-3 LRP patterning is severely affected from stage II onwards [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF].

Lateral root primordia boundary

To describe the organization of a LRP, the concepts of boundary (or flank/periphery) and centre domains are frequently used. LRP boundary and centre domains can be delimited by the ring of cells originated from tangential and radial cell division described above. These cells seem to act as a structure to support the rapidly developing LRP apex and are termed "buttress cells" [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF]; Figure 1). Their cell division pattern could be distinctively controlled since several cell cycle genes are preferentially expressed in the boundary [START_REF] Almeida Engler | Systematic analysis of cellcycle gene expression during Arabidopsis development[END_REF].

A few genes involved in the regulation of LRP boundary have been reported. The auxin transporter PIN6 gene is expressed specifically in the boundary of developing LRPs and is involved in auxin homeostasis during plant development. LRPs of seedlings overexpressing PIN6 undergo more rounds of anticlinal cell division, resulting in misshaped LRPs [START_REF] Cazzonelli | Role of the Arabidopsis PIN6 Auxin Transporter in Auxin Homeostasis and Auxin-Mediated Development[END_REF]. PUCHI encodes a transcription factor of the AP2/EREBP family involved in the control of LRP morphogenesis. Its expression is detected in the whole LRP of early stages and gradually confines to the flank domain of LRPs of later stages. Periphery cells of LRPs of puchi-1 mutant have extra anticlinal cell divisions, and some of those cells may be enlarged, suggesting that PUCHI regulates cell division pattern and cell differentiation during LRP development [START_REF] Hirota | The auxin-regulated AP2/EREBP gene PUCHI is required for morphogenesis in the early lateral root primordium of Arabidopsis[END_REF]. PUCHI functions downstream of auxin signalling and is proposed to co-act with LBD16/18 to control LRP development [START_REF] Hirota | The auxin-regulated AP2/EREBP gene PUCHI is required for morphogenesis in the early lateral root primordium of Arabidopsis[END_REF][START_REF] Kang | The AP2/EREBP gene PUCHI co-acts with LBD16/ASL18 and LBD18/ASL20 downstream of ARF7 and ARF19 to regulate lateral root development in arabidopsis[END_REF]. Its targets are currently unknown.

Loss of function of ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1/SDG27), a chromatin remodelling factor, impacts the coordination of cell division and cell differentiation in both primary root meristems and developing LRPs. Developing LRPs lacking ATX1 function are delayed, disorganized, and frequently exhibit enlarged flanking cells [START_REF] Napsucialy-Mendivil | Arabidopsis homolog of trithorax1 (ATX1) is required for cell production, patterning, and morphogenesis in root development[END_REF]. Still, the auxin signalling pattern in atx1 (as reported by DR5::GFP) looked similar to normal LRPs suggesting that ATX1 controls LRP patterning and cell proliferation independently of auxin response [START_REF] Napsucialy-Mendivil | Arabidopsis homolog of trithorax1 (ATX1) is required for cell production, patterning, and morphogenesis in root development[END_REF].

Similarly, loss of function of the transcription factor MYB36 causes misspecification of the LRP boundary [START_REF] Fernández-Marcos | Control of Arabidopsis lateral root primordium boundaries by MYB36[END_REF]. In the primary root meristem MYB36 is a target of SCR and a master regulator of endodermis cell differentiation [START_REF] Liberman | MYB36 regulates the transition from proliferation to differentiation in the Arabidopsis root[END_REF]. In LRP, MYB36 is expressed specifically in boundary cells and regulates genes involved in reactive oxygen species homeostasis. It is hence proposed that MYB36 regulates cell proliferation of LRP boundary domain by controlling their redox status [START_REF] Fernández-Marcos | Control of Arabidopsis lateral root primordium boundaries by MYB36[END_REF].

LRP shape progression through surrounding tissues and LRP emergence

As LRP cells divide, the LRP grows in contact with overlaying tissues, the first one being the endodermis. While the LRP develop from stage I to stage IV, the overlying endodermis, which contains lignified and suberized cell walls [START_REF] Naseer | Casparian strip diffusion barrier in Arabidopsis is made of a lignin polymer without suberin[END_REF][START_REF] Vishwanath | Suberin: biosynthesis, regulation, and polymer assembly of a protective extracellular barrier[END_REF], is subjected to important cell wall modifications (Vermeer et al., 2014). LRPs of mutants having increased deposition of suberin or lignin in the endodermis (i.e. more physical constraints) or plants in which the auxin-mediated response of endodermis has been impaired, are flatter compared to those of WT, leading to a delay in LRP emergence [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF]. By tracking the height of LRP during their development, [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF] showed that LRP heights increase gradually from stage I to IV, but display a dramatic increase in LRP height during stage V when LRP crosses the endodermis. That sudden change can be explained by cell expansion rather than cell division [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. The shape of LRP also changed from flat-topped to dome-shaped after breaking through the endodermis [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF][START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF].

The Casparian strips surrounding endodermis cells and linking them together form a supracellular network that is sturdy and resistant to pectinases [START_REF] Geldner | Casparian strips[END_REF], meaning that it is difficult for endodermal cells to separate to accommodate LRP penetration. Overlaying endodermal cells lose their cell volumes instead and become flatter. Plasma membranes of these cells are sometimes even fused together, but their integrity largely remains intact (Vermeer et al., 2014). Consequently, endodermal cells are separated at small breaking points just enough for the penetration of an LRP (Vermeer et al., 2014).

Although the volume loss mechanism of endodermal cells minimizes the impact of LRP on

Casparian strip integrity, it still can be compromised. A layer of suberin is deposited at the site of LRP penetration, covering both the endodermal cells and LRP surface (Li et al., 2017). This layer of suberin is thought to compensate to the damage of the Casparian strip, ensuring the function as an apoplastic barrier of the endodermis (von [START_REF] Wangenheim | Plant Biology: Building Barriers… in Roots[END_REF].

Although the cortex and epidermis pose less physical constraints to a developing LRP, they are also important for LRP development and participate actively to the process (reviewed in Stoeckle et al., 2018). Epidermal cells of two adjacent cell files are separated from one another to facilitate the progression of a LRP (Swarup et al., 2008). This separation is regulated by activity of cell-wall remodelling enzymes in cells directly overlaying a developing primordium.

Expression of these enzymes is regulated by an ARF7-LBD29-LAX3-LBD18 cascade (Swarup et al., 2008;Lee & Kim, 2013;[START_REF] Porco | Lateral root emergence in Arabidopsis is dependent on transcription factor LBD29 regulation of auxin influx carrier LAX3[END_REF] and other players such as BRS1 [START_REF] Deng | BRS1 function in facilitating lateral root emergence in arabidopsis[END_REF].

Water movement between cells is partially controlled by water channels called aquaporins integrated in cell membranes [START_REF] Li | Plant aquaporins: roles in plant physiology[END_REF]. A combination of experimental analysis of root tissue permeability to water and plasma membrane intrinsic aquaporins (PIPs) gene expression suggested that a complex spatio-temporal regulation of water fluxes across the root tissues, at least partially mediated by auxin, was critical for LRP emergence [START_REF] Péret | Auxin regulates aquaporin function to facilitate lateral root emergence[END_REF]. A modelling approach proposed that for optimal LRP emergence, auxin-mediated fine tuning of water transport could participate in increasing cell turgor in the LRP while decreasing it in the overlaying cortical and epidermal cells [START_REF] Péret | Auxin regulates aquaporin function to facilitate lateral root emergence[END_REF]. Moreover, during LRP development, tonoplast intrinsic aquaporin (TIP) protein levels are also regulated spatio-temporally, and defects in TIPs led to defects in LRP emergence. It was proposed that TIPs finely control the movement of water from surrounding tissues into cells at the base of LRP, allowing these cells to expand rapidly, thereby facilitating the emergence of LRPs [START_REF] Reinhardt | Tonoplast Aquaporins Facilitate Lateral Root Emergence[END_REF]. This model is consistent with the observation that the emergence of LRPs through overlying tissues is largely due to the rapid expansion of these basal cells [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF][START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. A recent study showed that during LRP formation, the circadian clock is re-phased, and this modulation regulates auxin-related genes and is required for LR emergence [START_REF] Voß | The circadian clock rephases during lateral root organ initiation in Arabidopsis thaliana[END_REF]. One possible explanation is that the re-phased circadian clock helps differentially control hydraulic properties of cells within LRP and in surrounding layers, thereby facilitating LRP emergence [START_REF] Voß | The circadian clock rephases during lateral root organ initiation in Arabidopsis thaliana[END_REF].

Connectivity between developing lateral root primordia and the primary root

The LR vasculature needs to connect to that of the primary root for proper functioning. Stele connection happens only when the LR already emerges as revealed by phloem unloading and stele marker expression studies [START_REF] Oparka | Symplastic communication between primary and developing lateral roots of Arabidopsis thaliana[END_REF][START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]. In LRPs, the connection with the primary root stele relies on symplastic connectivity, i.e. plasmodesmata.

Using the symplastic reporter pSUC2-GFP, it was shown that symplastic connection is present at early stages of LRP development, but is completely blocked at later stages until a functional stele is formed in emerged LRs [START_REF] Guyomarc'h | Early development and gravitropic response of lateral roots in Arabidopsis thaliana[END_REF][START_REF] Benitez-Alfonso | Symplastic Intercellular Connectivity Regulates Lateral Root Patterning[END_REF]. This change is correlated with the progressive deposition of callose at plasmodesmata, a process regulated by callose-degrading enzymes encoded by PdBG genes [START_REF] Benitez-Alfonso | Symplastic Intercellular Connectivity Regulates Lateral Root Patterning[END_REF].

Meristem formation and activation during lateral root formation

The root apical meristem is a specialized tissue ensuring root elongation and root cap regeneration through tightly regulated cell division and differentiation. In Arabidopsis, primary root apical meristem formation during embryogenesis and its post-embryonic maintenance have been thoroughly studied (reviewed in ten [START_REF] Hove | Building a plant: cell fate specification in the early Arabidopsis embryo[END_REF]Figure 3B). Arabidopsis root apical meristem displays a simple and stereotyped cellular organization with a central stem cell niche surrounding the organizing centre, called QC, and providing new progenitors for all the cell types of the root and the root cap (Figure 1). Stem cells, called initials, can be recognized from their location, close to the QC, and from their ability to produce progenitor cells through asymmetric cell division. Progenitor cells, or transit amplifying cells, can be recognized by the expression of cell fate specific marker genes as well as by proliferative cell divisions tending to conserve clonally related cell file structures. Key players during the embryonic root apical meristem formation and maintenance include auxin and its regulators, and transcription factors such as WUSCHEL RELATED HOMEOBOXs (WOXs), PLTs and SHR-SCR (Figure 4B). <Figure 4 near here>

Common molecular mechanisms controlling embryonic root apical meristem and LRP meristem formation

Recent studies have pointed to a parallel in the regulation of meristem formation and maintenance during embryogenesis and LRP development.

WUSCHEL RELATED HOMEOBOX 5 (WOX5), a marker for the primary root QC [START_REF] Haecker | Expression dynamics of WOX genes mark cell fate decisions during early embryonic patterning in Arabidopsis thaliana[END_REF], is also expressed during lateral root formation. The WOX5 function in columella stem cell maintenance appears to be conserved between primary root, lateral roots, and adventitious roots [START_REF] Sarkar | Conserved factors regulate signalling in Arabidopsis thaliana shoot and root stem cell organizers[END_REF]Tian et al., 2014a;[START_REF] Hu | Transcription Factors WOX11/12 Directly Activate WOX5/7 to Promote Root Primordia Initiation and Organogenesis[END_REF]. WOX5 is expressed at least from the stage IV-stage V transition onwards, in the 2 or 4 central cells presumptive of the QC anatomical organisation [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Rosspopoff | Direct conversion of root primordium into shoot meristem relies on timing of stem cell niche development[END_REF], although its expression may start even earlier, as suggested by other reporter constructs [START_REF] Ditengou | Mechanical induction of lateral root initiation in Arabidopsis thaliana[END_REF]Tian et al., 2014a;[START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. The importance of the stage IV-V transition for presumptive QC establishment is further supported by the onset of the QC-specific enhancer trap QC25 expression in the subapical cells of the developing primordium [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF].

Expression of WOX5 during embryonic root formation is dependent on the SHR-SCR module [START_REF] Sarkar | Conserved factors regulate signalling in Arabidopsis thaliana shoot and root stem cell organizers[END_REF]. In the embryo, SHR is transcribed in the root stele (vascular tissues and pericycle), and SHR controls SCR expression in the endodermis and QC in a non-cell autonomous fashion [START_REF] Nakajima | Intercellular movement of the putative transcription factor SHR in root patterning[END_REF][START_REF] Cui | An evolutionarily conserved mechanism delimiting SHR movement defines a single layer of endodermis in plants[END_REF][START_REF] Fisher | Uncovering the networks involved in stem cell maintenance and asymmetric cell division in the Arabidopsis root[END_REF]. Similarly, during LRP development, SHR is found in presumptive stele tissues, whereas SCR expression is confined to the endodermis precursor layer (Lucas et al., 2011b;[START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. Expression of SHR in the inner layer but not in the outer layer is an early patterning event in stage II LRP. Moreover, SCR expression seems to be activated by SHR, and is required for proper QC specification in the developing LRP [START_REF] Sabatini | SCARECROW is involved in positioning the stem cell niche in the Arabidopsis root meristem[END_REF][START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. SHR is also required for LRP initiation and development and for asymmetric divisions of cortex/endodermis initials in LRs (Lucas et al., 2011b).

PLTs, key players in embryonic root development, are also important for LRP formation. PLT1, PLT2 and PLT3 redundantly control embryonic root meristem establishment, since the triple mutant plt1plt2plt3 produces rootless seedlings and the plt1plt2 double mutant embryos only produce abnormal root meristems with no expression of QC marker genes [START_REF] Aida | The PLETHORA genes mediate patterning of the Arabidopsis root stem cell niche[END_REF].

PLT3, PLT5 and PLT7 are expressed as early as in stage I primordia where they control the asymmetric periclinal divisions giving rise to the stage II primordium. The activity of PLT3, PLT5 and PLT7 is necessary to switch on the differential expression of SHR and SCR in the two layers of the stage II primordium, as well as to induce expression of other PLTs including PLT1, PLT2 and PLT4 [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Interestingly, as the LRP progresses PLT5 expression is progressively confined to the base of the LRP, while the others are predominantly expressed in the central region comparable to the situation in the primary root meristem [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. In addition, the expression of PLTs is necessary to restrict auxin signalling maximum at the tip of the developing primordia by controlling expression of auxin transporter PIN genes, again similar to the situation in the primary root apical meristem [START_REF] Galinha | PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. As a result, in the plt3 plt5 plt7 mutant background LRPs are usually severely disorganized and contain enlarged cells. Very few of these LRPs emerge, indicating that LRPs of the plt3 plt5 plt7 mutant could not form a functional meristem [START_REF] Hofhuis | Phyllotaxis and rhizotaxis in Arabidopsis are modified by three plethora transcription factors[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Instead the double mutant plt1 plt2 can produce lateral roots but the meristem of these roots are disorganized and differentiate shortly after LR emergence, similar to the phenotype of the primary root apical meristem [START_REF] Aida | The PLETHORA genes mediate patterning of the Arabidopsis root stem cell niche[END_REF]. Together the data reveal a master role of PLT3, PLT5, and PLT7 genes in initiating the regulatory cascade that controls the functional patterning of the LRP centre. ARF5/MONOPTEROS (MP) is critical for embryonic root formation, since loss-of-function mp alleles, or dominant gain-of-function alleles of its inhibitor IAA12/BODENLOS, result in rootless seedlings (ten [START_REF] Hove | Building a plant: cell fate specification in the early Arabidopsis embryo[END_REF]. MP exerts its functions by positively controlling expression of multiple auxin transporter genes, including PIN1, PIN4, PIN7, AUX1 and LAX2, to trigger polar auxin accumulation necessary for embryonic root specification [START_REF] Weijers | Auxin triggers transient local signaling for cell specification in Arabidopsis embryogenesis[END_REF][START_REF] Hove | Building a plant: cell fate specification in the early Arabidopsis embryo[END_REF]. Recently, using a mutant background which allows studying the roles of MP post-embryonically, [START_REF] Krogan | The auxin response factor MONOPTEROS controls meristem function and organogenesis in both the shoot and root through the direct regulation of PIN genes[END_REF] demonstrated that MP directly binds to promoters of PIN1, PIN3, and PIN7 to regulate their expression levels and auxin distribution in developing LRP. Polar distribution of PIN1:GFP proteins in LRPs of the mutant also diminishes, coincident with the defects in LRP development. These mutant LRPs are disorganized and unable to develop after emergence, suggesting that a functional meristem is not established or maintained [START_REF] Krogan | The auxin response factor MONOPTEROS controls meristem function and organogenesis in both the shoot and root through the direct regulation of PIN genes[END_REF].

Experimental evidences described above point to a similarity in molecular mechanisms governing primary and lateral root development, although differences possibly linked to the distinct tissue context, can be noted. Especially, it is interesting to stress the contrasting roles of PLT3,5,7 and PLT1,2,4 in lateral root development, the former being required for the onset of expression of the latter, by the stage when WOX5 expression in the presumptive QC starts. In addition, specific regulatory network properties might be involved to organise the developing lateral root primordia and define its boundaries as well as its central domain, in which the root meristem can be patterned [START_REF] Lavenus | Inference of the Arabidopsis Lateral Root Gene Regulatory Network Suggests a Bifurcation Mechanism That Defines Primordia Flanking and Central Zones[END_REF].

Lateral root meristem activation

A first approach to determine the formation of a new root apical meristem in the developing LRP relies on the identification of a cellular pattern reminiscent of the primary root meristem cellular anatomy. Cytological analyses of developing LRP by [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF] highlighted conserved features in longitudinal sections of developing primordia. Especially, while a first sequence of anticlinal and periclinal cell divisions generated a regular four-layered primordium, subsequent cell division created a group of 2 square-shaped cells in the subapical position, which corresponds to the position of the future QC. This landmark cell division corresponds to stage V primordia. Subsequent cell divisions maintain this cellular organisation, and position of presumptive initials can soon be recognized, while the developing LRP grows through the cortex and epidermis cell layers [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF].

However, analysing cellular organization is not enough to determine if a meristem-like structure indeed functions like a meristem. In general, an active root meristem is recognized as a group of dividing and differentiating cells that is continuously replenished thanks to the maintenance of a stem cell niche. Therefore, applying this criterion to developing LRPs with the aim to identify a functional meristem requires either to analyse the expression of meristem cell fate markers and/or to precisely monitor dynamics in cell division and differentiation in developing LRPs.

Investigating cell division in developing primordia has long been difficult, but recent progresses in live imaging are now contributing to overcome this technical challenge [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Wangenheim | Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. In their detailed analysis of Arabidopsis LRP development, [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF] described conserved cell divisions creating the cellular organization similar to that of the primary root meristem around stage VI, but subsequent cell divisions were difficult to track. During LRP emergence, primordium apical cell number remains almost constant while basal cells quickly expand, thus supporting the model of cell elongationdriven LR emergence and post-emergence lateral root meristem activation [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF].

As reported earlier, analyses of marker gene expression in developing primordia support the hypothesis of QC being set as early as from stage V onwards, although WOX5 might already be expressed at earlier stages [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Whether these cells do actually behave like a stem cell niche organizing centre remains to be elucidated, since WOX5 stem-cell promoting activity was only shown in the primary and lateral root columella stem cells (Tian et al., 2014a;[START_REF] Pi | Organizer-Derived WOX5 Signal Maintains Root Columella Stem Cells through Chromatin-Mediated Repression of CDF4 Expression[END_REF]. Conversely, tracking initial stem cell fate remains difficult because no cell marker is available to clearly identify root "stem cell-ness" quality. However, SHR is expressed in inner cells abutting the WOX5-expressing cells in a comparable manner as in root meristem vascular initials (Figure 4A; [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF]. Comparably, SCR is expressed in cells flanking the presumptive QC, the characteristic position of cortex/endodermis initials [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. NAC domain transcription factors FEZ and SOMBRERO (SMB) are expressed in the primary root cap where they control the division of root cap stem cells [START_REF] Willemsen | The NAC Domain Transcription Factors FEZ and SOMBRERO Control the Orientation of Cell Division Plane in Arabidopsis Root Stem Cells[END_REF]. FEZ is also expressed in as early as stage VI LRP, at the very tip of the dome and in cells in contact with the presumptive QC, similar to the situation in mature root meristems [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Expression of SMB is detected in stage VI LRP, in the outermost layer of the primordium tip, consistent with its described role in specifying root cap progenitor cells [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Last, expression of the MYB related transcription factor WEREWOLF involved in epidermis specification [START_REF] Lee | WEREWOLF, a MYB-related protein in Arabidopsis, is a position-dependent regulator of epidermal cell patterning[END_REF] is also detected in the presumptive epidermis layer of emerging LRPs [START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Thus, many markers for root stem cell identity are already expressed in developing LRP before emergence, supporting the hypothesis that a complete root meristem stem cell niche is organized before LRP emergence.

As a functional test to identify meristematic activity, the ability of LRP of different stages to develop independently of exogenous auxin supply was assayed using excision protocols [START_REF] Laskowski | Formation of lateral root meristems is a two-stage process[END_REF]. LRPs with no less than 3 to 5 cell layers (which corresponds approximately to LRP of stages III to V) are able to develop after excision from the parental root [START_REF] Laskowski | Formation of lateral root meristems is a two-stage process[END_REF][START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF], in accordance with the report that LRPs at these stages are able to synthesize auxin IAA on their own [START_REF] Ljung | Sites and Regulation of Auxin Biosynthesis in Arabidopsis Roots[END_REF]. Detailed analysis of LRP development by [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF] supports the model that LRP development is a biphasic process, comprising an early morphogenesis phase and a later meristem formation phase.

Importantly the transition happens at around stage V, coincident with the shift from bilateral symmetry to radial symmetry of LRPs [START_REF] Lucas | Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues[END_REF][START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF], and with the onset of expression of both WOX5 and QC25, typical markers of root QC, in the central cells of the second outermost layer [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Rosspopoff | Direct conversion of root primordium into shoot meristem relies on timing of stem cell niche development[END_REF]. In the root apical meristem, a QC is specified at the overlap between SHR-SCR and PLTs, which are activated by local auxin signaling maximum [START_REF] Aida | The PLETHORA genes mediate patterning of the Arabidopsis root stem cell niche[END_REF][START_REF] Sablowski | The dynamic plant stem cell niches[END_REF]. If this criterion is applied to lateral roots, then the WOX5-and QC25-positive cells in stage IV-V LRPs can be considered a QC [START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. [START_REF] Rosspopoff | Direct conversion of root primordium into shoot meristem relies on timing of stem cell niche development[END_REF] suggested that these QC marker positive-cells constitute a functional stem cell niche that is required for the direct conversion of a LRP into a shoot meristem during the artificial cytokinin-induced shoot regeneration process.

Taken together, the data suggests the progressive establishment of a stem cell niche organization from the stage II, with SCR/SHR-dependent outer layer specification, to lateral root emergence, with the induction of epidermis and root cap identities. A critical step in this de novo root meristem organogenesis process occurs at the stage IV-V transition, when the primordium breaks through the overlying endodermis layer, develops a radial symmetry centred on a QC-specific marker expressing niche, and acquires autonomy relative to the auxin fluxes from the parent root.

Interestingly, this newly established root stem cell niche may only be active after LR emergence [START_REF] Malamy | Organization and cell differentiation in lateral roots of Arabidopsis thaliana[END_REF]. The characterization of the aberrant lateral root formation 3 (alf3) mutant, that is unable to sustain LR growth after emergence unless exogenous auxin is supplied [START_REF] Celenza | A pathway for lateral root formation in Arabidopsis thaliana[END_REF], also supports the hypothesis that a major transition in LRP meristem activity takes place at LR emergence.

LRP organogenesis as a common basis for organ regeneration from callus

Organ regeneration is a process of de novo organogenesis of shoots or roots from wounded or detached plant tissues. It is widely used in plant tissue culture to multiply plants quickly. Tissue culture usually goes through two steps: first callus formation, and then root or shoot organogenesis induction using different combinations of phytohormones. More and more expressed in multiple subepidermal cell layers comparable to the stele (Sugimoto et al., 2010).

The outer layer of the callus expresses the epidermis-specific markers MERISTEM LAYER 1 and GLABRA2, and even displays root cap functional characteristics, such as the presence of statoliths [START_REF] Atta | Pluripotency of Arabidopsis xylem pericycle underlies shoot regeneration from root and hypocotyl explants grown in vitro[END_REF]Sugimoto et al., 2010). Moreover, the QC marker WOX5 whose expression is activated during LRP development (Tian et al., 2014a;[START_REF] Goh | Quiescent center initiation in the Arabidopsis lateral root primordia is dependent on the SCARECROW transcription factor[END_REF][START_REF] Rosspopoff | Direct conversion of root primordium into shoot meristem relies on timing of stem cell niche development[END_REF] is also expressed in a single subepidermal cell layer in the callus, although its expression range is expanded probably because of the disturbed auxin gradient provided by the callus induction medium (Sugimoto et al., 2010). These analyses indicate that callus shares important characteristics with the root apical meristem and the LRP. Indeed, transcriptomic analyses showed that callus forming from various organs is enriched in root tipexpressed genes. In addition, there is a large overlap in genes upregulated in root, cotyledon and petal explants during callus formation, indicating that this process shares common mechanisms in these different contexts. However, the number of genes upregulated in aerial explants are much higher than those in root explants, suggesting that callus formation from aerial organs requires intermediate steps (Sugimoto et al., 2010).

Callus formation also depends on the auxin signalling module comprising ARF7, ARF19 and their LBD targets (LBD16, LBD17, LBD19, LBD29) which plays critical roles in controlling LRP initiation, development and emergence [START_REF] Okushima | ARF7 and ARF19 regulate lateral root formation via direct activation of LBD/ASL genes in Arabidopsis[END_REF][START_REF] Lee | LBD18/ASL20 regulates lateral root formation in combination with LBD16/ASL18 downstream of ARF7 and ARF19 in Arabidopsis[END_REF][START_REF] Goh | The establishment of asymmetry in Arabidopsis lateral root founder cells is regulated by LBD16/ASL18 and related LBD/ASL proteins[END_REF]. LBD genes (LBD16, LBD17, LBD18, LBD29) are also strongly induced in both shoot and root explants cultivated in callus induction medium [START_REF] Fan | LATERAL ORGAN BOUNDARIES DOMAIN transcription factors direct callus formation in Arabidopsis regeneration[END_REF]. These LBDs physically interact with the transcription factor AtbZIP59 to control callus formation [START_REF] Xu | Control of auxin-induced callus formation by bZIP59-LBD complex in Arabidopsis regeneration[END_REF].

Overexpression of these genes is sufficient to induce spontaneous callus formation at various degrees and positions in the seedlings [START_REF] Fan | LATERAL ORGAN BOUNDARIES DOMAIN transcription factors direct callus formation in Arabidopsis regeneration[END_REF][START_REF] Xu | Control of auxin-induced callus formation by bZIP59-LBD complex in Arabidopsis regeneration[END_REF]. Conversely, suppression of LBD function reduces LR formation from primary roots and almost abolishes callus formation capability of root explants [START_REF] Fan | LATERAL ORGAN BOUNDARIES DOMAIN transcription factors direct callus formation in Arabidopsis regeneration[END_REF]. Like in LRP development, LBD genes also act downstream of auxin via ARF9 and ARF19 in the context of callus formation [START_REF] Fan | LATERAL ORGAN BOUNDARIES DOMAIN transcription factors direct callus formation in Arabidopsis regeneration[END_REF]Lee et al., 2017).

Interestingly, the formation of callus-like structures in leaf vascular tissues induced by root-knot nematodes also depends on LBD16 [START_REF] Olmo | Molecular Transducers from Roots Are Triggered in Arabidopsis Leaves by Root-Knot Nematodes for Successful Feeding Site Formation: A Conserved Post-Embryogenic De novo Organogenesis Program[END_REF]. Another LBD gene, LBD29, which regulates LR initiation through maintaining cell division competence of pericycle cells [START_REF] Feng | LBD29 regulates the cell cycle progression in response to auxin during lateral root formation in Arabidopsis thaliana[END_REF], also controls callus formation on callus induction medium [START_REF] Xu | Genome-Wide Identification of Arabidopsis LBD29 Target Genes Reveals the Molecular Events behind Auxin-Induced Cell Reprogramming during Callus Formation[END_REF]. During callus formation, LBD29 activates genes of different functional categories such as transcriptional regulation, ROS and lipid metabolism, and cell wall hydrolysis. Overexpression of some putative targets induces spontaneous callus formation at various degrees, similar to the phenotype of LBD29-overexpressing plants [START_REF] Xu | Genome-Wide Identification of Arabidopsis LBD29 Target Genes Reveals the Molecular Events behind Auxin-Induced Cell Reprogramming during Callus Formation[END_REF].

Callus formation is an important intermediate step for de novo organ regeneration by hormonal treatment. In this procedure, explants are first incubated in auxin-rich callus induction medium to induce the formation of calli that acquire pluripotency for subsequent shoot regeneration. When transferred to a shoot induction medium that has high cytokinin-to-auxin ratio, some callus cells transform into shoot progenitors that will eventually develop into shoots [START_REF] Kareem | PLETHORA genes control regeneration by a two-step mechanism[END_REF].

PLTs, key regulators in LRP and root apical meristem formation [START_REF] Galinha | PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF], also play pivotal roles in hormone-induced organ-regeneration. Like in a developing LRP, expression of PLT3, PLT5 and PLT7 genes is up-regulated during callus formation and shoot regeneration [START_REF] Kareem | PLETHORA genes control regeneration by a two-step mechanism[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF]. Single mutants in these genes are able to regenerate shoots in shoot induction medium, but the regeneration capability is completely lost in the triple mutant. Moreover, overexpression of PLT5 or PLT7 is enough to induce shoot regeneration in the plt3 plt5 plt7 mutant background in hormone-free medium. This data indicates that PLT5 and PLT7 transcription factors are necessary and sufficient for shoot regeneration from callus. Expression of key root stem cell maintenance regulators, including SCR, PLT1 and PLT2 is upregulated in callus originated from wild type shoot and root explants, but not detected in plt3 plt5 plt7 calli [START_REF] Kareem | PLETHORA genes control regeneration by a two-step mechanism[END_REF]. PLT3, PLT5 and PLT7 transcription factors also positively regulate the expression of the auxin efflux carrier PIN1 gene during callus formation. Altogether, the data points to a common regulatory pathway involving PLT genes in LRP formation and de novo organ regeneration: in both processes (i) PLT genes are required, and (ii) PLT3, PLT5 and PLT7 regulate PLT1 and PLT2 and also PIN1 expression in a similar manner [START_REF] Kareem | PLETHORA genes control regeneration by a two-step mechanism[END_REF][START_REF] Du | PLETHORA transcription factors orchestrate de novo organ patterning during Arabidopsis lateral root outgrowth[END_REF].

As described for LR FC specification and LRP formation, chromatin-remodelling factors also play critical roles in callus formation. ARABIDOPSIS TRITHORAX-RELATED 2 (ATXR2), a trithorax group protein as ATX1 mentioned above, modifies target gene expression by deposition of positive histone marks. ATXR2 binds to the promoter of LBD16 and LBD29 with the help of ARF7 and ARF19 transcription factors to induce permissive chromatin conformation on these loci. Consistent with the critical roles of LBDs in callus formation, the ability of leaf explants to form calli is significantly reduced in the atxr2 mutant background and enhanced in an ATRX2 overexpressing line (Lee et al., 2017). Although it is not clear if this regulation of ATXR2 on LBDs is also true in LRP formation, lateral root production in the atxr2 mutant is significantly reduced compared to the wild type [START_REF] Lee | ATXR2 as a core regulator of de novo root organogenesis[END_REF]. Finally, subunits of the Polycomb repressive complex 2 (PRC2), which negatively regulates LR FC specification, were shown to inhibit callus formation given that single or combined mutants of these subunits produce callus spontaneously in tissue culture [START_REF] Chanvivattana | Interaction of Polycomb-group proteins controlling flowering in Arabidopsis[END_REF][START_REF] Bouyer | Polycomb Repressive Complex 2 Controls the Embryo-to-Seedling Phase Transition[END_REF]. Interestingly, although not exactly in the context of LRP development, callus formation and adventitious root formation from leaf explants are demonstrated to share a common genetic pathway. In Callus Induction Medium (CIM), leaf explants produce callus through two steps: founder cell specification and callus formation [START_REF] Yu | Auxin Control of Root Organogenesis from Callus in Tissue Culture[END_REF]. In the first step, pericycle-like (procambium) cells highly express WOX11, a WOX5-related transcription factor that acts redundantly with WOX12 to convert competent cells into callus founder cells. WOX11 and WOX12 then activate the expression of LBD16 and WOX5 to induce founder cell division to form a callus [START_REF] Liu | WOX11 and 12 Are Involved in the First-Step Cell Fate Transition during de Novo Root Organogenesis in Arabidopsis[END_REF][START_REF] Hu | Transcription Factors WOX11/12 Directly Activate WOX5/7 to Promote Root Primordia Initiation and Organogenesis[END_REF][START_REF] Sheng | Non-canonical WOX11 -mediated root branching contributes to plasticity in Arabidopsis root system architecture[END_REF]. This two-step mechanism is conserved in both monocot and dicot plants [START_REF] Hu | Divergent regeneration-competent cells adopt a common mechanism for callus initiation in angiosperms[END_REF]. The genetic pathway comprising of WOX11, WOX12 and WOX5, along with other important genetic factors such as PLT1, PLT2 and SHR, is also involved in adventitious root founder cell specification and hormone-free root regeneration from leaf explants [START_REF] Liu | WOX11 and 12 Are Involved in the First-Step Cell Fate Transition during de Novo Root Organogenesis in Arabidopsis[END_REF][START_REF] Hu | Transcription Factors WOX11/12 Directly Activate WOX5/7 to Promote Root Primordia Initiation and Organogenesis[END_REF][START_REF] Bustillo-Avendaño | Regulation of Hormonal Control, Cell Reprogramming and Patterning during De Novo Root Organogenesis[END_REF][START_REF] Sheng | Non-canonical WOX11 -mediated root branching contributes to plasticity in Arabidopsis root system architecture[END_REF]. This newly unravelled molecular mechanisms for callus formation can help bridge the gaps between LR and adventitious root formation.

General conclusions

Root system architecture greatly impacts plant growth and crop yield, and root branching contributes to a major extent to root system development. Root branching consists in a strikingly robust event of post-embryonic organogenesis that progressively generates, thanks to coordinated proliferation of pericycle-derived founder cells, a new functional root meristem including a stem cell niche. Major regulators of cell fate and cell behaviour, especially cell cycle, are involved in triggering and then controlling this organogenesis process. Specific transcription factors, chromatin modifiers, and signalling pathways impact gene expression in a precise time and space dependent manner, although we are still far from having elucidated all their interactions and understanding the properties of the entire network. Importantly non-cell autonomous signals, such as mobile peptides, directional fluxes of the plant hormone auxin, and transcription factors able to move through plasmodesmata, mediate cell-to-cell coordination across tissues and the emergence of developmental patterns. Moreover, de novo root meristem formation associated to root branching shares common regulatory mechanisms together with root meristem specification in the embryo and plant regeneration from calli, raising interesting evodevo as well as biotechnological perspectives. However, many questions are still open regarding key developmental events during LRP organogenesis. How pericycle cell competency for root organogenesis is precisely regulated remains unclear. In addition, the precise molecular mechanisms underlying pericycle cell priming, prebranch site formation and founder cell specification are unknown. Last, the regulatory network properties controlling the organisation of a new root apical meristem are not understood. Hopefully, the comparison of root formation from embryonic, post-embryonic, and calli tissues will help to unravel the fundamental properties of this organogenesis program.

Captions for figures

1.

Figure 1. Arabidopsis primary root and lateral root meristems. Schematic organization of the apical meristem of Arabidopsis primary root (A) and emerged lateral root (B). Cell types of primary root apical meristem and presumptive cell types of lateral root apical meristems are indicated in the colour legend. In root apical meristems, the stem cells are called "initials" and the organizing centre is termed "quiescent centre" (QC).

Figure 2 .

 2 Figure 2. Key events during lateral root primordium initiation and their regulators

Figure 4 .

 4 Figure 4. Distribution patterns of some key regulators in different developmental contexts.

(EMF2) displayed increased density of LR FCs and emerged LRs, suggesting that the PRC2 complex might inhibit LR FC specification[START_REF] Gu | A Histone H3 Lysine-27 Methyltransferase Complex Represses Lateral Root Formation in Arabidopsis thaliana[END_REF]. CURLY LEAF is expressed in the

Acknowledgements

Work by D. C. T., L. L. and S. G. is supported by the Institute of Research for Development, the University of Montpellier, the University of Science and Technology of Hanoi and the French National Research Agency (ANR-17-CE13-0004-01). We thank the anonymous reviewer for useful comments on the manuscript and apologize to authors whose work could not be cited due to space limitation.

evidence indicate that the process of organ regeneration employs similar regulatory mechanisms to that of LRP formation, especially at the first step of callus formation (Figure 4). First of all, callus and LR formation share a similar cellular origin. When cultivated in auxin-rich medium, callus develops from pericycle cells in root explants and from cells surrounding vasculature bundles in other aerial organs (Sugimoto et al., 2010). The alf4-1 mutant is defective in pericycle cell divisions, consequently unable to produce any LRs. Consistent with this, callus formation from alf4-1 root explants is blocked when cultivated in multiple combinations of auxin and cytokinin concentrations (Sugimoto et al., 2010). Interestingly, callus formation from aerial organs, including cotyledons and petals, is also inhibited in the alf4-1 mutant. Close inspection of the pericycle marker line J0121 showed GFP expression in cells surrounding the midvein of the cotyledons and the petals. This expression gradually diminishes when callus formation progresses, similar to what happens in root pericycle cells during LRP and callus formation in roots [START_REF] Laplaze | GAL4-GFP enhancer trap lines for genetic manipulation of lateral root development in Arabidopsis thaliana[END_REF][START_REF] Che | Developmental steps in acquiring competence for shoot development in Arabidopsis tissue culture[END_REF]Sugimoto et al., 2010). These pericycle-like cells are also present in leaves and are involved in hormone-free root regeneration [START_REF] Liu | WOX11 and 12 Are Involved in the First-Step Cell Fate Transition during de Novo Root Organogenesis in Arabidopsis[END_REF][START_REF] Bustillo-Avendaño | Regulation of Hormonal Control, Cell Reprogramming and Patterning during De Novo Root Organogenesis[END_REF]. This data indicates that pericycle and pericycle-like cells are essential for both LRP formation and callus formation from explants of various origins.

Contrary to the previous perception that callus is an unorganized mass of undifferentiated cells, callus is actually an organized structure resembling a LRP. Both callus and LRP originate from pericycle or pericycle-like cells, and then develop into structures of multiple cell layers [START_REF] Atta | Pluripotency of Arabidopsis xylem pericycle underlies shoot regeneration from root and hypocotyl explants grown in vitro[END_REF]Sugimoto et al., 2010). Cell identity markers in the root apical meristem and LRP are also expressed in callus in comparable domains (Figure 4). For example, pSCR::GFP, a marker for endodermal and QC cells in the primary root meristem, is expressed in a single cell layer under the epidermis, while pSHR::SHR:GFP, the marker for stele, endodermal and QC cells, is Vermeer, J.E.M., Wangenheim, D. von, Barberon, M., et al. (2014) A Spatial Accommodation by Neighboring Cells Is Required for Organ Initiation in Arabidopsis. Science, 343, 178-183. Vernoux, T., Brunoud, G., Farcot, E., et al. (2014) The auxin signalling network translates 64 3. The inner layer of stage II LRP will eventually develop into ground tissues and pericycle (grey), while the outer layer develops into the endodermis, cortex, epidermis and root cap (light blue).

From stage IV onwards, some central cells start expressing QC markers. For simplicity, the