1. Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Mianato-ku, Tokyo 108-8639, Japan
2. Division of Cancer Genomics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Mianato-ku, Tokyo 108-8639, Japan
3. Division of Gene Expression and Regulation, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Mianato-ku, Tokyo 108-8639, Japan
4. CREST, Japan Science and Technology Corporation
5. PRESTO, Japan Science and Technology Corporation
6. Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku,Kyoto 606-8509, Japan
7. Laboratory Animal Center, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan

Correspondence to: Tadaomi Takenawa^1,2 Correspondence and requests for materials should be addressed to T.T. (Email: takenawa@ims.u-tokyo.ac.jp).

Abstract

WAVE2, a protein related to Wiskott–Aldrich syndrome protein, is crucial for Rac-induced membrane ruffling, which is important in cell motility^{1, 2, 3, 4}. Cell movement is essential for morphogenesis, but it is unclear how cell movement is regulated or related to morphogenesis. Here we show the physiological functions of WAVE2 by disruption of the WAVE2 gene in mice. WAVE2 was expressed predominantly in vascular endothelial cells during embryogenesis. WAVE2^-/- embryos showed haemorrhages and died at about embryonic day 10. Deficiency in WAVE2 had no significant effect on vasculogenesis, but it decreased sprouting and branching of endothelial cells from existing vessels during angiogenesis. In WAVE2^-/- endothelial cells, cell polarity formed in response to vascular endothelial growth factor, but the formation of lamellipodia at leading edges and capillaries was severely impaired. These findings indicate that WAVE2-regulated actin reorganization might be required for proper cell movement and that a lack of functional WAVE2 impairs angiogenesis in vivo.