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

Genes Dev. 2003 Jan 15;17(2):295-309. doi: 10.1101/gad.1022203.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Line
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Polarity / genetics
  • Cell Polarity / physiology
  • Dishevelled Proteins
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins
  • Frizzled Receptors
  • Gastrula / cytology*
  • Gastrula / metabolism*
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA / genetics
  • RNA / metabolism
  • Signal Transduction
  • Wnt Proteins
  • Xenopus / embryology*
  • Xenopus / genetics
  • Xenopus / metabolism*
  • Xenopus Proteins
  • Zebrafish Proteins*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • DVL1 protein, Xenopus
  • Dishevelled Proteins
  • Drosophila Proteins
  • Frizzled Receptors
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • dsh protein, Drosophila
  • RNA
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • rac GTP-Binding Proteins
  • rho GTP-Binding Proteins