Modular control of vertebrate axis segmentation in time and space

How the timing of development is linked to organismal size is a longstanding question. Although numerous studies have reported a correlation of temporal and spatial traits, the developmental or selective constraints underlying this link remain largely unexplored. We address this question by studying the periodic process of embryonic axis segmentation in-vivo in Oryzias fish. Interspecies comparisons reveal that the timing of segmentation correlates to segment, tissue and organismal size. Segment size in turn scales according to tissue and organism size. To probe for underlying causes, we genetically hybridised two closely related species. Quantitative analysis in ~600 phenotypically diverse F2 embryos reveals a decoupling of timing from size control, while spatial scaling is preserved. Using developmental quantitative trait loci (devQTL) mapping we identify distinct genetic loci linked to either the control of segmentation timing or tissue size. This study demonstrates that a developmental constraint mechanism underlies spatial scaling of axis segmentation, while its spatial and temporal control are dissociable modules

A propos de gradients et d'oscillations: le rôle de la voie de signalisation Wnt dans la formation des somites au cours du développement embryonnaire

A fundamental characteristic of all vertebrates is the metameric organization of their body plan, best exemplified by the vertebral column. This organization originates during embryonic development and the emergence of the vertebrae precursor, the somites, which form from the paraxial presomitic mesoderm (PSM). The discovery of oscillatory transcriptional activity of the Notch-signaling pathway within the PSM supports the existence of an embryological clock, the segmentation clock, which is responsible in controlling the periodic formation of somites. Here, I present the discovery of oscillatory mRNA expression of Axin2, a target of the Wnt-signaling pathway, in the PSM. This establishes a novel link between Wnt signaling and the segmentation clock. I then describe the generation of a two-photon, real-time imaging technology that allows visualizing segmentation clock activity in realtime in living mouse embryos. This enables us to directly measure oscillation parameters in the PSM. Finally, I describe the discovery of a -catenin protein gradient in the PSM. Using conditional gene targeting experiments, we establish that this gradient controls PSM maturation and differentiation. Moreover, this gradient represents a permissive signal that allows segmentation clock activity to occur. Based on the results presented, I propose a novel model for somite formation.Une caractéristique fondamentale des vertébrés est leur organisation métamerique, visible au niveau de la colonne vertébrale. Cette organisation se met en place au cours du développement embryonnaire et l'émergence des précurseurs des vertèbres, les somites, formés à partir du mésoderm paraxial présomitique (PSM). Depuis la découverte d'une activité transcriptionelle oscillatoire de la voie de signalisation Notch dans le PSM, on propose que cette activité oscillatoire représente l'action d'une horloge embryonnaire, l'horloge de segmentation, responsable de contrôler la formation des somites de façon périodique. Dans cette étude, je présente la découverte d'une nouvelle association de la voie Wnt avec l'horloge de segmentation en décrivant l'activité oscillatoire de Axin2, une cible de la voie Wnt, dans le PSM. Ensuite, j'ai mise en place un system d'imagerie biphoton qui nous permet d'observer l'action de l'horloge de segmentation en temps réel et in vivo dans les embryons de souris. Ce système permet de mesurer directement les paramètres des oscillations. Ultérieurement je décris la découverte d'un gradient d'expression de la protéine -caténine dans le PSM. A l'aide d'expériences de recombinaisons homologues conditionnelles nous avons déterminé que ce gradient de - caténine contrôle la maturation et différentiation des cellules dans le PSM. De plus, ce gradient constitue un signal essentiel et permissif pour les oscillations de l'horloge de segmentation. En conclusion, je propose un nouveau modèle de mise en place des somites incorporant les résultats présentés

About gradients and oscillations (the role of the Wnt-signaling pathway in somite formation during embryonic development)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Dynamic signal encoding—From cells to organisms

AbstractEncoding information at the level of signal dynamics is characterized by distinct features, such as robustness to noise and high information content. Currently, a growing number of studies are unravelling the functional importance of signalling dynamics at the single cell level. In addition, first insights are emerging into how the principles of dynamic signal encoding apply to a multicellular context, such as development. In this review, we will first discuss general concepts of information transmission via signalling dynamics and recent experimental examples focusing on underlying principles, including the role of intracellular network topologies. How multicellular organisms use temporal modulation of specific signalling pathways, such as signalling gradients or oscillations, to faithfully control cell fate decisions and pattern formation will also be addressed. Finally, we will consider how technical advancements in the detection and perturbation of signalling dynamics contribute to reshaping our understanding of dynamic signalling in developing organisms

More Than Patterning—Hox Genes and the Control of Posterior Axial Elongation

Hox genes are well known for their evolutionarily conserved role in patterning the body axis. Now, Young et al. in this issue of Developmental Cell present evidence that at least in mouse embryos Hox genes do more, namely controlling the process of axis formation itself