title: Apico-basal forces exerted by apoptotic cells drive epithelium folding.
abstract: 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.
authors.affiliation: 1] Université de Toulouse, UPS, LBCMCP, F-31062 Toulouse, France [2] CNRS, LBCMCP, F-31062 Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Monier
authors.affiliation: 1] Université de Toulouse, UPS, LBCMCP, F-31062 Toulouse, France [2] CNRS, LBCMCP, F-31062 Toulouse, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gettings
authors.affiliation: DamCB, Data Analysis and Modelling for Cell Biology, 13005 Marseille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gay
authors.affiliation: 1] Université de Toulouse, UPS, LBCMCP, F-31062 Toulouse, France [2] CNRS, LBCMCP, F-31062 Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mangeat
authors.affiliation: 1] Université de Toulouse, UPS, LBCMCP, F-31062 Toulouse, France [2] CNRS, LBCMCP, F-31062 Toulouse, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Schott
authors.affiliation: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Guarner
authors.affiliation: 1] Université de Toulouse, UPS, LBCMCP, F-31062 Toulouse, France [2] CNRS, LBCMCP, F-31062 Toulouse, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Suzanne
mesh_terms: D022005:Adherens Junctions / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016764:Cell Polarity; D048430:Cell Shape; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000196:embryology*; D008954:Models, Biological; D009024:Morphogenesis; D024462:Myosin Type II / Q000378:metabolism
chemical_list: D024462:Myosin Type II