WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

Catherine Yan, Narcisa Martinez-Quiles, Sharon Eden, Tomoyuki Shibata, Fuminao Takeshima, Reiko Shinkura, Yuko Fujiwara, Roderick Bronson, Scott B. Snapper, Marc W. Kirschner, Raif Geha, Fred S. Rosen, Frederick W. Alt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

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.

Original languageAmerican English
Pages (from-to)3602-3612
Number of pages11
JournalEMBO Journal
Volume22
Issue number14
DOIs
StatePublished - 15 Jul 2003
Externally publishedYes

Keywords

  • Actin polymerization
  • Lamellipodium
  • Rho GTPase
  • WASP-related protein
  • WAVE

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