title: Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation.
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 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 beta-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.
authors.affiliation: Laboratory of Molecular Genetics, National Institutes of Child Health and Human Development, Bethesda, Maryland 20892-2790, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
authors.forename: Igor B
authors.initials: IB
authors.lastname: Dawid
authors.forename: Xi
authors.initials: X
authors.lastname: He
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D005775:Gastrula / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C000606588:dsh protein, Drosophila; D012313:RNA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins