title: Rapid epithelial-sheet sealing in the Caenorhabditis elegans embryo requires cadherin-dependent filopodial priming.
abstract: BACKGROUND
  During embryonic development, epithelia with free edges must join together to create continuous tissues that seal the interior of the organism from the outside environment; failure of epithelial sealing underlies several common human birth defects. Sealing of epithelial sheets in embryos can be extremely rapid, dramatically exceeding the rate of adherens junction formation by epithelial cells in culture or during healing of epithelial wounds. Little is known about the dynamic redistribution of cellular junctional components during such events in living embryos.
  
  
  RESULTS
  We have used time-lapse, multiphoton laser-scanning microscopy and green fluorescent protein fusion proteins to analyze the sealing of the Caenorhabditis elegans epidermis in living embryos. Rapid recruitment of alpha-catenin to sites of filopodial contact between contralateral migrating epithelial cells, concomitant with clearing of cytoplasmic alpha-catenin, resulted in formation of nascent junctions; this preceded the formation of mature junctions. Surprisingly, upon inactivation of the entire cadherin-catenin complex, only adhesive strengthening between filopodia was reproducibly affected. Other ventral epidermal cells, which did not extend filopodia and appeared to seal along the ventral midline by coordinated changes in cell shape, successfully adhered in the absence of these proteins.
  
  
  CONCLUSIONS
  We propose that 'filopodial priming' - prealignment of bundled actin in filopodia combined with the rapid recruitment of alpha-catenin from cytoplasmic reserves at sites of filopodial contact - accounts for the rapid rate of sealing of the embryonic epidermis of C. elegans. Filopodial priming may provide a general mechanism for rapid creation of adherens junctions during epithelial-sheet sealing in embryos.
authors.affiliation: Program in Cellular and Molecular Biology University of Wisconsin-Madison 1117 W Johnson Street, Madison, Wisconsin, 53706, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Raich
authors.forename: C
authors.initials: C
authors.lastname: Agbunag
authors.forename: J
authors.initials: J
authors.lastname: Hardin
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D004848:Epithelium / Q000196:embryology; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D011554:Pseudopodia / Q000502:physiology*; D051178:alpha Catenin
chemical_list: C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; D051178:alpha Catenin; D049452:Green Fluorescent Proteins