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, 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 triggered Rho-associated kinase-dependent ectopic apical constriction, marked by apical accumulation of phospho-MLC, γ-tubulin and F-actin in superficial ectoderm, and stimulated apical protrusive activity of deep ectoderm cells. Together, our observations demonstrate novel functions of GEF-H1 in morphogenetic movements leading to neural tube closure.
- Revision received February 20, 2014.