Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation

  1. Raymond Habas1,2,
  2. Igor B. Dawid1, and
  3. Xi He2,3
  1. 1Laboratory of Molecular Genetics, National Institutes of Child Health and Human Development, Bethesda, Maryland 20892-2790, USA; 2Division of Neuroscience, Children's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA

Abstract

Wnt/Frizzled (Fz) signaling controls cell polarity/movements during vertebrate gastrulation via incompletely defined mechanisms. We demonstrated previously that Wnt/Fz activation of Rho, a GTPase and regulator of cytoskeletal architecture, is essential for vertebrate gastrulation. Here we report that in mammalian cells andXenopus embryos, Wnt/Fz signaling coactivates Rho and Rac, another GTPase and distinct regulator of cytoskeletal architecture. Wnt/Fz activation of Rac is independent of Rho and mediates Wnt/Fz activation of Jun N-terminal kinase (JNK). Dishevelled (Dvl), a cytoplasmic protein downstream of Fz, forms a Wnt-induced complex with Rac independent of the Wnt-induced Dvl–Rho complex. Depletion or inhibition of Rac function perturbs Xenopus gastrulation without affecting Wnt/Fz activation of the Rho or β-catenin pathway. We propose that parallel activation of Rac and Rho pathways by Wnt/Fz signaling is required for cell polarity and movements during vertebrate gastrulation.

Keywords

Footnotes

  • 3 Corresponding author.

  • E-MAIL xi.he{at}tch.harvard.edu; FAX (617) 734-1646.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1022203.

    • Received July 9, 2002.
    • Accepted November 15, 2002.
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