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PMID: 12533515 Published · ppublish English Comparative Study Journal Article 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.

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

Genes & development ·Vol. 17 ·No. 2 ·2003-01-15 ·Pages 295-309

Habas R, Dawid IB, He X

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Cell Line Cell Movement/genetics,physiology Cell Polarity/genetics,physiology Dishevelled Proteins Drosophila/embryology,genetics,metabolism Drosophila Proteins Frizzled Receptors Gastrula/cytology,metabolism Humans JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases/metabolism Models, Biological Phosphoproteins/genetics,metabolism Proteins/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism RNA/genetics,metabolism Signal Transduction Wnt Proteins Xenopus/embryology,genetics,metabolism Xenopus Proteins Zebrafish Proteins rac GTP-Binding Proteins/genetics,metabolism rho GTP-Binding Proteins/genetics,metabolism
Chemicals
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
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Habas Raymond
Laboratory of Molecular Genetics, National Institutes of Child Health and Human Development, Bethesda, Maryland 20892-2790, USA.
Dawid Igor B
He Xi
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1022203
Published
2003-01-15
Pages
295-309
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC195976
Subset
IM
Grants
NINDS NIH HHS · T32 NS007473 · United States
NINDS NIH HHS · NS07473 · United States
External Links
PubMed source DOI: 10.1101/gad.1022203 PMC Full Text View journal details
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