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  • The EMBO Journal (2008) 27, 606 - 617
  • doi:10.1038/emboj.2008.9

Published online: 7 February 2008

WGEF activates Rho in the Wnt–PCP pathway and controls convergent extension in Xenopus gastrulation

Kosuke Tanegashima1, Hui Zhao1 and Igor B Dawid1

  1. Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

Correspondence to:

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

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.

  • Keywords:

    • convergent extension,
    • gastrulation,
    • GEF,
    • Wnt–PCP,
    • Xenopus