GEF-H1 functions in apical constriction and cell intercalations and is essential for vertebrate neural tube closure

Keiji Itoh, Olga Ossipova, Sergei Y. Sokol

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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, c-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.

Original languageEnglish
Pages (from-to)2542-2553
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number11
DOIs
StatePublished - Jun 2014

Keywords

  • Apical constriction
  • Cell intercalation
  • Epiboly
  • Lfc
  • Morphogenesis
  • Myosin II
  • Neural tube closure
  • Rho GTPases
  • Xenopus

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