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J Cell Sci 2014 Jun 01;127Pt 11:2542-53. doi: 10.1242/jcs.146811.
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GEF-H1 functions in apical constriction and cell intercalations and is essential for vertebrate neural tube closure.

Itoh K , Ossipova O , Sokol SY .

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.

PubMed ID: 24681784
PMC ID: PMC4038946
Article link: J Cell Sci
Grant support: [+]

Species referenced: Xenopus
Genes referenced: actl6a arhgef2 h1-3 mlc1 myc rab11a rho rho.2 rhoa shroom3 sox2 srf
Morpholinos: arhgef2 MO2 arhgef2 MO3 arhgef2 MO4

Article Images: [+] show captions
References [+] :
Aijaz, Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. 2005, Pubmed