The dystroglycan: Nestled in an adhesome during embryonic development

AbstractInvertebrate and vertebrate development relies on complex processes that require many coordinated cell functions including cell adhesion, migration, proliferation and polarization. These processes depend on tissues and are spatio-temporally regulated by specific interactions between cells and between cells and the extracellular matrices. The dystroglycan, a transmembrane receptor that binds multiple extracellular matrix proteins, is expressed from oogenesis to organogenesis. There are increasing data suggesting that the axis, consisting of extracellular component–dystroglycan–cytoplasmic proteins, controls both the adhesion of cells to matrices as well as the transduction of signals coming from or directed to matrices. In this article, we review current advances leading to consider that the dystroglycan is a key protein nestled in an adhesome involved in mechanisms of cell adhesion during embryonic development

Ephrin-mediated restriction of ERK1/2 activity delimits the number of pigment cells in the Ciona CNS

AbstractRecent evidence suggests that ascidian pigment cells are related to neural crest-derived melanocytes of vertebrates. Using live-imaging, we determine a revised cell lineage of the pigment cells in Ciona intestinalis embryos. The neural precursors undergo successive rounds of anterior–posterior (A–P) oriented cell divisions, starting at the blastula 64-cell stage. A previously unrecognized fourth A–P oriented cell division in the pigment cell lineage leads to the generation of the post-mitotic pigment cell precursors. We provide evidence that MEK/ERK signals are required for pigment cell specification until approximately 30min after the final cell division has taken place. Following each of the four A–P oriented cell divisions, ERK1/2 is differentially activated in the posterior sister cells, into which the pigment cell lineage segregates. Eph/ephrin signals are critical during the third A–P oriented cell division to spatially restrict ERK1/2 activation to the posterior daughter cell. Targeted inhibition of Eph/ephrin signals results in, at neurula stages, anterior expansion of both ERK1/2 activation and a pigment cell lineage marker and subsequently, at larval stages, supernumerary pigment cells. We discuss the implications of these findings with respect to the evolution of the vertebrate neural crest

Snail mediates medial–lateral patterning of the ascidian neural plate

International audienceThe ascidian neural plate exhibits a regular, grid-like arrangement of cells. Patterning of the neural plate across the medial–lateral axis is initiated by bilateral sources of Nodal signalling, such that Nodal signalling induces expression of lateral neural plate genes and represses expression of medial neural plate genes. One of the earliest lateral neural plate genes induced by Nodal signals encodes the transcription factor Snail. Here, we show that Snail is a critical downstream factor mediating this Nodal-dependent patterning. Using gain and loss of function approaches, we show that Snail is required to repress medial neural plate gene expression at neural plate stages and to maintain the lateral neural tube genetic programme at later stages. A comparison of these results to those obtained following Nodal gain and loss of function indicates that Snail mediates a subset of Nodal functions. Consistently, overexpression of Snail can partially rescue a Nodal inhibition phenotype. We conclude that Snail is an early component of the gene regulatory network, initiated by Nodal signals, that patterns the ascidian neural plate

Co-expression of Foxa.a, Foxd and Fgf9/16/20 defines a transient mesendoderm regulatory state in ascidian embryos

International audienceIn many bilaterian embryos, nuclear b-catenin (nb-catenin) promotes mesendoderm over ectoderm lineages. Although this is likely to represent an evolutionary ancient developmental process, the regulatory architecture of nb-catenin-induced mesendoderm remains elusive in the majority of animals. Here, we show that, in ascidian embryos, three nb-catenin transcriptional targets, Foxa.a, Foxd and Fgf9/16/20, are each required for the correct initiation of both the mesoderm and endoderm gene regulatory networks. Conversely, these three factors are sufficient, in combination, to produce a mesendoderm ground state that can be further programmed into mesoderm or endoderm lineages. Importantly, we show that the combinatorial activity of these three factors is sufficient to reprogramme developing ectoderm cells to mesendoderm. We conclude that in ascidian embryos, the transient mesendoderm regulatory state is defined by co-expression of Foxa.a, Foxd and Fgf9/16/20

Analyse du rôle du dystroglycane dans les processus d'épithélialisation lors du développement précoce du Xénope

Les molécules d adhérence, qui interviennent dans les interactions entre les cellules et la matrice extracellulaire, jouent un rôle majeur dans l organisation et le maintien de l architecture des tissus, ainsi que dans les processus qui conduisent à l épithélialisation au cours du développement précoce. Parmi ces molécules, le dystroglycane est une protéine transmembranaire qui lie préférentiellement la laminine. Il est connu pour avoir un rôle dans la stabilité du sarcolemme des muscles squelettiques, la morphogenèse des tissus neuroépithéliaux, l organisation du cytosquelette, ainsi que dans la polarisation et la signalisation cellulaire. L objectif de cette thèse a été d étudier la fonction du dystroglycane lors de deux évènements d organogenèse chez le Xénope : la formation du rein embryonnaire et la différenciation de l épiderme. Pour cela, nous avons réalisé une perte de fonction du dystroglycane en utilisant soit un dominant négatif, soit une stratégie antisens par injection de morpholinos. Nos travaux ont montré, in vivo, que le dystroglycane joue un rôle dans l assemblage de la laminine. Sans cet assemblage, la lame basale qui est une structure spécialisée de la matrice extracellulaire propre aux tissus épithéliaux ne peut pas se mettre en place. Nous avons également mis en évidence l implication du dystroglycane dans le processus d épithélialisation. De plus, les résultats obtenus suggèrent que le dystroglycane pourrait être impliqué dans différentes voies de signalisation, notamment dans celle régulant la prolifération cellulaire. Enfin, nous avons montré, pour la première fois in vivo, que la transcription du dystroglycane était sous le contrôle de la voie de signalisation Notch au moins lors de l épithélialisation de l'épiderme.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Patterning of brain precursors in ascidian embryos

International audienceIn terms of their embryonic origins, the anterior and posterior parts of the ascidian central nervous system (CNS) are associated with distinct germ layers. The anterior part of the sensory vesicle, or brain, originates from ectoderm lineages following a neuro-epidermal binary fate decision. In contrast, a large part of the remaining posterior CNS is generated following neuro-mesodermal binary fate decisions. Here, we address the mechanisms that pattern the anterior brain precursors along the medial-lateral axis (future dorsal-ventral) at neural plate stages. Our functional studies show that Nodal signals are required for induction of lateral genes including Delta-like, Snail, Msxb and Trp. Delta-like/Notch signalling induces intermediate (Gsx) over medial (Meis) gene expression in intermediate cells, while the combinatorial action of Snail and Msxb prevents the expression of Gsx in lateral cells. We conclude that despite the distinct embryonic lineage origins within the larval CNS, the mechanisms that pattern neural precursors are remarkably similar

Model of neural induction in the ascidian embryo

Abstract How cell specification can be controlled in a reproducible manner is a fundamental question in development biology. In ascidians, a group of marine invertebrate chordates, geometry plays a key role in achieving this control. Here, we use mathematical modeling to demonstrate that geometry dictates the neural-epidermal cell fate choice in the 32-cell stage ascidian embryo by a two-step process involving first the modulation of ERK signaling and second, the expression of the neural marker gene, Otx . The model describes signal transduction by the ERK pathway that is stimulated by FGF and repressed by ephrin, and ERK-mediated control of Otx gene expression, which involves both an activator and an inhibitor of transcription. Considering the measured area of cell surface contacts with FGF- or ephrin-expressing cells as inputs, the solutions of the model reproduce the experimental observations about ERK activation and Otx expression in the different cells under normal and perturbed conditions. Sensitivity analyses and computations of Hill coefficients allow to quantify the robustness of the specification mechanism controlled by cell surface area and to identify the respective role played by each signaling input. Simulations also predict in which conditions the dual control of gene expression by an activator and an inhibitor that are both under the control of ERK can induce a robust ON/OFF control of neural fate induction. Author summary The development of a single cell zygote into a multicellular embryo occurs thanks to the combination of cell division and cell specification. The latter process corresponds to the progressive acquisition by the embryonic cells of their final physiological and functional characteristics, which rely on well-defined signaling-controlled genetic programs. The origin of the great robustness of cell specification remains poorly understood. Here, we address this question in the framework of the embryonic neural fate induction in ascidians, which are marine invertebrates. At the 32-cells stage, four cells identified by their precise location in the embryo adopt neural fate. On the basis of experimental observations, we develop a mathematical model that predicts that the choice between the neural or epidermal fate is controlled by the cell surface areas of the cells in contact with two antagonistic signals, FGF and ephrin. Our findings provide a computational confirmation of the major role played by the geometry of the embryo in controlling cell lineage acquisition during ascidian development

An adhesome comprising laminin, dystroglycan and myosin IIA is required during notochord development in Xenopus laevis.

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Cell geometry, signal dampening, and a bimodal transcriptional response underlie the spatial precision of an ERK-mediated embryonic induction

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An ERF transcription factor participates in the bimodal transcriptional response of an ERK-target gene during ascidian neural induction

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