1. WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.
- Author
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M.W. Kirschner, C. Yan, R. Geha, N. Martinez-Quiles, S. Eden, F.S. Rosen, T. Shibata, F.W. Alt, F. Takeshima, R. Shinkura, Y. Fujiwara, S.B. Snapper, and R. Bronson
- Subjects
GENETIC mutation ,DWARFISM - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2003