Apico-basal forces exerted by apoptotic cells drive epithelium folding

© 2015 Macmillan Publishers Limited. All rights reserved. Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.Agence Nationale de la Recherche (ANR), Fondation de la Recherche et de l’Innovation The´rapeutique en Cance´rologie (RITC) and the University of Toulouse.Peer Reviewe

Le rôle de la voie JNK dans la transdifférenciation et la morphogenèse épithéliale chez Drosophila melanogaster

La fermeture dorsale de l épiderme de l embryon de drosophile est un modèle morpho génétique de migration et de soudure épithéliale apparenté à la cicatrisation. L activation de la voie JK spécifiquement dans les cellules bordant les deux feuillets épithéliaux, appelées cellules de la marge , est essentielle pour orchestrer le mouvement. Un crible génomique nous a permis d identifier des nouvelles cibles transcriptionnelles de la voie JNK, dont le gène CG5835. L analyse de son expression non-uniforme dans la marge montre que, contrairement à ce qui avait été admis, l activité de la voie JNK n est pas homogène, mais suit le patron de l épiderme qui est divisé en unités fonctionnelles ou segments . Ceux-ci sont composés de deux lignées de cellules non miscibles, formant ainsi deux compartiments, l un antérieur et l autre postérieur. Parallèlement, nous montrons qu au niveau des frontières segmentales, la voie JNK induit la transdifférenciation d une cellule antérieure de la marge, nommée cellule Mixer , en cellule postérieure, et ceci grâce à l expression de novo du déterminant postérieur Engrailed. Ce processus conduit à un surprenant remodelage des frontières segmentales au cours duquel la cellule Mixer change de compartiment. Ceci est accompagné de l intercalation de cellules au niveau de la marge, laquelle est tendue par un câble d actine, créant ainsi une zone de dilatation ? L ensemble de ce travail a changé notre vision de la fermeture dorsale que nous concevons désormais come la migration coordonnée de segments, dotés chacun d une région plastique dont le rôle serait éventuellement de relâcher la tension dans la marge.NICE-BU Sciences (060882101) / SudocSudocFranceF

JNK signalling controls remodelling of the segment boundary through cell reprogramming during Drosophila morphogenesis. PLoS Biol 8: e1000390

Segments are fundamental units in animal development which are made of distinct cell lineages separated by boundaries. Although boundaries show limited plasticity during their formation for sharpening, cell lineages make compartments that become tightly restricted as development goes on. Here, we characterize a unique case of breaking of the segment boundary in late drosophila embryos. During dorsal closure, specific cells from anterior compartments cross the segment boundary and enter the adjacent posterior compartments. This cell mixing behaviour is driven by an anterior-to-posterior reprogramming mechanism involving de novo expression of the homeodomain protein Engrailed. Mixing is accompanied by stereotyped local cell intercalation, converting the segment boundary into a relaxation compartment important for tension-release during morphogenesis. This process of lineage switching and cell remodelling is controlled by JNK signalling. Our results reveal plasticity of segment boundaries during late morphogenesis and a role for JNK-dependen

Le dernier sursaut des cellules mourantes

Peer Reviewe