Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation
Open accessAbstract
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 β-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.
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The second branch of signaling requires the DEP domain of Dsh and activates the Rac GTPase, independent of Daam1, and activated Rac stimulates JNK activity.
“The second branch of signaling requires the DEP domain of Dsh and activates the Rac GTPase. This activation is independent of Daam1 and activated Rac in turn stimulates JNK activity.66,84”
From Wnt signal transduction pathways (2008) · cites this paper as [66]
Many components of non-canonical pathway, including Dsh, Fz, Daam1, Rho, Rac, Prickle and Strabismus, were shown to disrupt convergent extension.
“Many other components of non-canonical pathway were also shown to disrupt convergent extension, including Dsh, Fz, Daam1, Rho, Rac, Prickle and Strabismus.65–74”
From Wnt signal transduction pathways (2008) · cites this paper as [66]
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Self-citation
- Authors
- Habas, R., Dawid, I. B., & He, X.
- Affiliations
- National Institutes of Health (US)
- Boston Children's Hospital (US)
- Corresponding author
- He, Xi
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-01-15
- Volume
- 17
- Issue
- 2
- Pages
- 295-309
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC195976
- OpenAlex
- W2099353036
- Cited by
- 603
- References
- 71
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 22 · 2021: 26 · 2020: 11 · 2019: 15 · 2018: 11 · 2017: 20 · 2016: 16 · 2015: 26 · 2014: 27 · 2013: 23 · 2012: 35
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- W. M. Keck Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS07473, T32NS007473)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Wnt/Frizzled signaling, Rac, Rho GTPases, Dishevelled, Jun N-terminal kinase, cell polarity, cell migration, cytoskeleton regulation, Xenopus embryo, β-catenin signaling
- MeSH terms
- Dishevelled Proteins, Animals, Cell Line, Cell Movement, Drosophila, Gastrula, Humans, Models, Biological, Phosphoproteins, Proteins, Proto-Oncogene Proteins, RNA, Xenopus, Signal Transduction, Cell Polarity, rho GTP-Binding Proteins, rac GTP-Binding Proteins, Mitogen-Activated Protein Kinases, Drosophila Proteins, Xenopus Proteins, Zebrafish Proteins, JNK Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Wnt Proteins, Frizzled Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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