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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Cell Line
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Cell Movement / genetics
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Cell Movement / physiology
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Cell Polarity / genetics
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Cell Polarity / physiology
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Dishevelled Proteins
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Drosophila / embryology
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Drosophila / genetics
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Drosophila / metabolism
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Drosophila Proteins
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Frizzled Receptors
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Gastrula / cytology*
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Gastrula / metabolism*
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Humans
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases / metabolism
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Models, Biological
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA / genetics
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RNA / metabolism
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Signal Transduction
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Wnt Proteins
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Xenopus / embryology*
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Xenopus / genetics
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Xenopus / metabolism*
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Xenopus Proteins
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Zebrafish Proteins*
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism*
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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DVL1 protein, Xenopus
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Dishevelled Proteins
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Drosophila Proteins
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Frizzled Receptors
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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dsh protein, Drosophila
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RNA
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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rac GTP-Binding Proteins
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rho GTP-Binding Proteins