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  • The EMBO Journal (2003) 22, 3602 - 3612
  • doi:10.1093/emboj/cdg350

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

Catherine Yan1,2,3, Narcisa Martinez-Quiles4,5, Sharon Eden6, Tomoyuki Shibata7,8, Fuminao Takeshima7,8, Reiko Shinkura9, Yuko Fujiwara9,10, Roderick Bronson11, Scott B. Snapper7,8, Marc W. Kirschner6, Raif Geha4,5, Fred S. Rosen1,2,5 and Frederick W. Alt1,2,3,5,9

  1. Center for Blood Research, 200 Longwood Avenue, Boston, MA 02115, USA
  2. Department of Medicine, Children's Hospital, Boston, MA 02115, USA
  3. Department of Genetics, Harvard Medical School, Boston, MA 02115 USA
  4. Division of Immunology, Children's Hospital, Boston, MA 02115, USA
  5. Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA
  6. Department of Cell Biology, Harvard Medical School, Boston, MA 02115 USA
  7. Department of Medicine, Harvard Medical School, Boston, MA 02115 USA
  8. Gastrointestinal Unit (Medical Services) and the Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02115, USA
  9. Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115, USA
  10. Division of Hematology and Oncology, Children's Hospital, Boston, MA 02115, USA
  11. Department of Pathology, Harvard Medical School, Boston, MA 02115 USA

Correspondence to:

Frederick W. Alt, E-mail: alt@enders.tch.harvard.edu

Received 23 January 2003; Accepted 21 May 2003; Revised 4 April 2003

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.

  • Keywords:

    • actin polymerization,
    • lamellipodium,
    • Rho GTPase,
    • WASP-related protein,
    • WAVE