title: GEF-H1 functions in apical constriction and cell intercalations and is essential for vertebrate neural tube closure.
abstract: Rho family GTPases regulate many morphogenetic processes during vertebrate development including neural tube closure. Here we report a function for GEF-H1/Lfc/ArhGEF2, a RhoA-specific guanine nucleotide exchange factor that functions in neurulation in Xenopus embryos. Morpholino-mediated depletion of GEF-H1 resulted in severe neural tube defects, which were rescued by GEF-H1 RNA. Lineage tracing of GEF-H1 morphants at different developmental stages revealed abnormal cell intercalation and apical constriction, suggesting that GEF-H1 regulates these cell behaviors. Molecular marker analysis documented defects in myosin II light chain (MLC) phosphorylation, Rab11 and F-actin accumulation in GEF-H1-depleted cells. In gain-of-function studies, overexpressed GEF-H1 induced Rho-associated kinase-dependent ectopic apical constriction - marked by apical accumulation of phosphorylated MLC, γ-tubulin and F-actin in superficial ectoderm - and stimulated apical protrusive activity of deep ectoderm cells. Taken together, our observations newly identify functions of GEF-H1 in morphogenetic movements that lead to neural tube closure.
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Keiji
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ossipova
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA sergei.sokol@mssm.edu.
authors.forename: Sergei Y
authors.initials: SY
authors.lastname: Sokol
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication; D022081:Cell Surface Extensions / Q000235:genetics; D002478:Cells, Cultured; D003250:Constriction; D004625:Embryo, Nonmammalian; D009024:Morphogenesis / Q000235:genetics; D060172:Morpholinos / Q000235:genetics; D024462:Myosin Type II / Q000378:metabolism; D054259:Neural Tube / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport / Q000235:genetics; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000199:Actins; D060172:Morpholinos; D024462:Myosin Type II; D064067:Rho Guanine Nucleotide Exchange Factors; D014404:Tubulin; D029867:Xenopus Proteins; D020691:rab GTP-Binding Proteins; D054460:rho-Associated Kinases; D000099193:rab11 GTP-Binding Proteins; C000597170:GEF-H1 protein, Xenopus
keywords: Apical constriction; Cell intercalation; Epiboly; Lfc; Morphogenesis; Myosin II; Neural tube closure; Rho GTPases; Xenopus