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Vol. 17, No. 2, pp. 295-309, January 15, 2003
1 Laboratory of Molecular Genetics, National Institutes of
Child Health and Human Development, Bethesda, Maryland 20892-2790, USA;
2 Division of Neuroscience, Children's Hospital, Department
of Neurology, Harvard Medical School,
Boston, Massachusetts 02115, USA
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 and
Xenopus 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 
-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.
[Key Words: Wnt; Frizzled; Rac; Rho; gastrulation; vertebrates]
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