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| Subject Categories:
Signal Transduction
| Development
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The EMBO Journal
(2008) 27, 606–617, doi:10.1038/emboj.2008.9 Published online 7 February 2008
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WGEF activates Rho in the Wnt–PCP pathway and controls convergent extension in Xenopus gastrulation
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Kosuke Tanegashima, Hui Zhao and Igor B Dawid
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Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
To whom correspondence should be addressed
Igor B Dawid, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel.: +1 301 496 4448; Fax: +1 301 496 0243; E-mail: idawid@mail.nih.gov
Received 15 August 2007; Accepted 10 January 2008; Published online 7 February 2008.
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| Abstract |
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| The Wnt–PCP (planar cell polarity, PCP) pathway regulates cell polarity and convergent extension movements during axis formation in vertebrates by activation of Rho and Rac, leading to the re-organization of the actin cytoskeleton. Rho and Rac activation require guanine nucleotide-exchange factors (GEFs), but the identity of the GEF involved in Wnt–PCP-mediated convergent extension is unknown. Here we report the identification of the weak-similarity GEF (WGEF) gene by a microarray-based screen for notochord enriched genes, and show that WGEF is involved in Wnt-regulated convergent extension. Overexpression of WGEF activated RhoA and rescued the suppression of convergent extension by dominant-negative Wnt-11, whereas depletion of WGEF led to suppression of convergent extension that could be rescued by RhoA or Rho-associated kinase activation. WGEF protein preferentially localized at the plasma membrane, and Frizzled-7 induced colocalization of Dishevelled and WGEF. WGEF protein can bind to Dishevelled and Daam-1, and deletion of the Dishevelled-binding domain generates a hyperactive from of WGEF. These results indicate that WGEF is a component of the Wnt–PCP pathway that connects Dishevelled to Rho activation. |
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| Keywords: convergent extension, gastrulation, GEF, Wnt–PCP, Xenopus |
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