WAVE2, a protein related to Wiskott–Aldrich syndrome protein, is crucial for Rac-induced membrane ruffling, which is important in cell motility1,2,3,4. 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.
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Miki, H., Suetsugu, S. & Takenawa, T. WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J. 17, 6932–6941 (1998)
Suetsugu, S., Miki, H. & Takenawa, T. Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex. Biochem. Biophys. Res. Commun. 260, 296–302 (1999)
Miki, H., Yamaguchi, H., Suetsugu, S. & Takenawa, T. IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 408, 732–735 (2000)
Miki, H. & Takenawa, T. WAVE2 serves a functional partner of IRSp53 by regulating its interaction with Rac. Biochem. Biophys. Res. Commun. 293, 93–99 (2002)
Small, J. V., Stradal, T., Vignal, E. & Rottner, K. The lamellipodium: where motility begins. Trends Cell Biol. 12, 112–120 (2002)
Rickert, P., Weiner, O. D., Wang, F., Bourne, H. R. & Servant, G. Leukocytes navigate by compass: roles of PI3Kγ and its lipid products. Trends Cell Biol. 10, 466–473 (2000)
Chung, C. Y., Funamoto, S. & Firtel, R. A. Signaling pathways controlling cell polarity and chemotaxis. Trends Biochem. Sci. 26, 557–566 (2001)
Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629–635 (2002)
Takenawa, T. & Miki, H. WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J. Cell Sci. 114, 1801–1809 (2001)
Risau, W. Mechanisms of angiogenesis. Nature 386, 671–674 (1997)
Takakura, N. et al. Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. Immunity 9, 677–686 (1998)
Takakura, N. et al. A role for hematopoietic stem cells in promoting angiogenesis. Cell 102, 199–209 (2000)
Yamaguchi, H., Miki, H. & Takenawa, T. Neural Wiskott–Aldrich syndrome protein is involved in hepatocyte growth factor-induced migration, invasion, and tubulogenesis of epithelial cells. Cancer Res. 62, 2503–2509 (2002)
Connolly, J. O., Simpson, N., Hewlett, L. & Hall, A. Rac regulates endothelial morphogenesis and capillary assembly. Mol. Biol. Cell 13, 2474–2485 (2002)
Hashi, H. et al. Compartmentalization of Peyer's patch anlagen before lymphocyte entry. J. Immunol. 166, 3702–3709 (2001)
Shimada, T., Nakamura, M., Kitahara, Y. & Sachi, M. Surface morphology of chemically-digested Purkinje fibers of the goat heart. J. Electron Microsc. (Tokyo) 32, 187–196 (1983)
We thank A. Miyawaki (BSI, Riken, WAKO, Saitama, Japan) for the gift of green fluorescent protein variant (venus).
The authors declare that they have no competing financial interests.
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Yamazaki, D., Suetsugu, S., Miki, H. et al. WAVE2 is required for directed cell migration and cardiovascular development. Nature 424, 452–456 (2003). https://doi.org/10.1038/nature01770
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