title: Ring formation drives invagination of the vulva in Caenorhabditis elegans: Ras, cell fusion, and cell migration determine structural fates.
abstract: Directed cell rearrangements occur during gastrulation, neurulation, and organ formation. Despite the identification of developmental processes in which invagination is a critical component of pattern formation, little is known regarding the underlying cellular and molecular details. Caenorhabditis elegans vulval epithelial cells undergo morphological changes that generate an invagination through the formation of seven stacked rings. Here, we study the dynamics of ring formation during multivulva morphogenesis of a let-60/ras gain-of-function mutant as a model system to explore the cellular mechanisms that drive invagination. The behavior of individual cells was analyzed in a let-60/ras mutant by three-dimensional confocal microscopy. We showed that stereotyped cell fusion events occur within the rings that form functional and nonfunctional vulvae in a let-60/ras mutant. Expression of let-60/ras gain-of-function results in abnormal cell migration, ectopic cell fusion, and structural fate transformation. Within each developing vulva the anterior and posterior halves develop autonomously. Contrary to prevailing hypotheses which proposed three cell fates (1 degrees, 2 degrees, and 3 degrees), we found that each of the seven rings is a product of a discrete structural pathway that is derived from arrays of seven distinct cell fates (A, B, C, D, E, F, and H). We have also shown how autonomous ring formation is the morphogenetic force that drives invagination of the vulva.
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Shemer
authors.forename: R
authors.initials: R
authors.lastname: Kishore
authors.forename: B
authors.initials: B
authors.lastname: Podbilewicz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002459:Cell Fusion; D019070:Cell Lineage; D002465:Cell Movement; D005260:Female; D005455:Fluorescent Antibody Technique; D005836:Genitalia, Female / Q000196:embryology*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009024:Morphogenesis; D009154:Mutation; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C066646:let-60 protein, C elegans; D018631:ras Proteins