title: Spatial control of active CDC-42 during collective migration of hypodermal cells in Caenorhabditis elegans.
abstract: Collective epithelial cell migration requires the maintenance of cell-cell junctions while enabling the generation of actin-rich protrusions at the leading edge of migrating cells. Ventral enclosure of Caenorhabditis elegans embryos depends on the collective migration of anterior-positioned leading hypodermal cells towards the ventral midline where they form new junctions with their contralateral neighbours. In this study, we characterized the zygotic function of RGA-7/SPV-1, a CDC-42/Cdc42 and RHO-1/RhoA-specific Rho GTPase-activating protein, which controls the formation of actin-rich protrusions at the leading edge of leading hypodermal cells and the formation of new junctions between contralateral cells. We show that RGA-7 controls these processes in an antagonistic manner with the CDC-42's effector WSP-1/N-WASP and the CDC-42-binding proteins TOCA-1/2/TOCA1. RGA-7 is recruited to spatially distinct locations at junctions between adjacent leading cells, where it promotes the accumulation of clusters of activated CDC-42. It also inhibits the spreading of these clusters towards the leading edge of the junctions and regulates their accumulation and distribution at new junctions formed between contralateral leading cells. Our study suggests that RGA-7 controls collective migration and junction formation between epithelial cells by spatially restricting active CDC-42 within cell-cell junctions.
authors.affiliation: Department of Chemistry, Pharmaqam, Biomed, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Ouellette
authors.affiliation: Department of Chemistry, Pharmaqam, Biomed, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Martin
authors.affiliation: Department of Chemistry, Pharmaqam, Biomed, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Germain
authors.initials: G
authors.lastname: Lacoste-Caron
authors.affiliation: Department of Chemistry, Pharmaqam, Biomed, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Hamiche
authors.affiliation: Department of Chemistry, Pharmaqam, Biomed, Université du Québec à Montréal, Montréal, Québec, Canada jenna.sarah@uqam.ca.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jenna
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D008954:Models, Biological; D011554:Pseudopodia / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000378:metabolism*
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C081779:cdc-42 protein, C elegans; D049452:Green Fluorescent Proteins; D019204:GTP-Binding Proteins
keywords: Caenorhabditis elegans; Cdc42; Rho GAP; collective migration; epithelial; morphogenesis; ventral enclosure