WAVE2 deficiency reveals distinct roles in embryogenesis and Rac‐mediated actin‐based motility
Open accessAbstract
The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement.
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Mice lacking other critical actin-regulatory genes such as Rac1 and the WAVE complex component Nap1 show similar developmental abnormalities, resulting in death during early embryogenesis; deletion of Rac1 and Nap1 causes death during gastrulation at E7.5 and E9, respectively.
“Similar developmental abnormalities, resulting in death during early embryogenesis, have been observed in mice lacking other critical actin-regulatory genes such as Rac1 and the WAVE complex component Nap1. Deletion of these genes in the mouse cause death during gastrulation at E7.5 and E9, respectively.69, 70, 71”
From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [69]
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Cites
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Yoon, K.-J., Nguyen, H. N., Ursini, G., Zhang, F., Kim, N.-S., Wen, Z., Makri, G., Nauen, D., Shin, J. H., Park, Y., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.05.003 · Cited by 240 · see citing works
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- Authors
- Yan, C., Martinez‐Quiles, N., Eden, S., Shibata, T., Takeshima, F., Shinkura, R., Fujiwara, Y., Bronson, R., Snapper, S. B., Kirschner, M. W., Geha, R., Rosen, F. S., & Alt, F. W.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- Corresponding author
- Alt, Frederick W.
- Venue
- The EMBO Journal
- Published
- 2003-07-15
- Volume
- 22
- Issue
- 14
- Pages
- 3602-3612
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC165620
- OpenAlex
- W2119421814
- Cited by
- 186
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 11 · 2012: 13
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Ministerio de Economía y Competitividad
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- WAVE2, Wiskott-Aldrich syndrome, Rac, Rho GTPases, actin cytoskeleton, embryonic development, embryonic fibroblasts, embryonic stem cells, cell motility, platelet-derived growth factor, lamellipodium formation, actin polymerization
- MeSH terms
- Actins, Animals, Biopolymers, Cell Line, Cell Movement, Cytoskeleton, Embryo, Mammalian, Fibroblasts, Microfilament Proteins, Mutation, Pseudopodia, RNA, Stem Cells, Wiskott-Aldrich Syndrome, Gene Deletion, Mice, Knockout, Protein Isoforms, rac GTP-Binding Proteins, Wiskott-Aldrich Syndrome Protein Family, Mice
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