title: Epiboly generates the epidermal basal monolayer and spreads the nascent mammalian skin to enclose the embryonic body.
abstract: Epiboly is a morphogenetic process that is employed in the surface ectoderm of anamniotes during gastrulation to cover the entire embryo. We propose here that mammals also utilise this process to expand the epidermis and enclose the body cavity and spinal cord with a protective surface covering. Our data supports a model whereby epidermal spreading is driven by the primary establishment of the epidermal basal progenitor monolayer through radial cell intercalation of a multi-layered epithelium towards the basal lamina. By using a suspension organotypic culture strategy, we find that this process is fibronectin-dependent and autonomous to the skin. The radial cell rearrangements that drive epidermal spreading also require ROCK activity but are driven by cell protrusions and not myosin II contractility. Epidermal progenitor monolayer formation and epidermal spreading are delayed in Crash mice, which possess a dominant mutation in Celsr1, an orthologue of the core planar cell polarity (PCP) Drosophila protein Flamingo (also known as Stan). We observe a failure of ventral enclosure in Crash mutants suggesting that defective epidermal spreading might underlie some ventral wall birth defects.
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Guys Tower, Kings College London, London SE1 1UL, UK.
authors.forename: Eleni
authors.initials: E
authors.lastname: Panousopoulou
authors.affiliation: Wolfson-CARD, Kings College London, London SE1 1UL, UK.
authors.forename: Carl
authors.initials: C
authors.lastname: Hobbs
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunts House, Kings College London, London SE1 1UL, UK.
authors.forename: Ivor
authors.initials: I
authors.lastname: Mason
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Guys Tower, Kings College London, London SE1 1UL, UK.
authors.forename: Jeremy B A
authors.initials: JB
authors.lastname: Green
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunts House, Kings College London, London SE1 1UL, UK caroline.formstone@kcl.ac.uk.
authors.forename: Caroline J
authors.identifier: 0000-0002-5936-5149
authors.initials: CJ
authors.lastname: Formstone
mesh_terms: D000818:Animals; D001215:Asparaginase / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000166:cytology / Q000196:embryology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000502:physiology*
chemical_list: D001215:Asparaginase
keywords: Cell polarity; Celsr1; Epiboly; Epidermal morphogenesis; Progenitor monolayer