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First published online October 24, 2008
doi: 10.1242/10.1242/dev.022475

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Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis

Yung Hae Kim, Huiqing Hu, Salvador Guevara-Gallardo, Michael T. Y. Lam^*, Shun-Yin Fong and Rong A. Wang

Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.

Author for correspondence (e-mail: rong.wang{at}ucsfmedctr.org)

Accepted 17 September 2008

A mutual coordination of size between developing arteries and veins is essential for establishing proper connections between these vessels and, ultimately, a functional vasculature; however, the cellular and molecular regulation of this parity is not understood. Here, we demonstrate that the size of the developing dorsal aorta and cardinal vein is reciprocally balanced. Mouse embryos carrying gain-of-function Notch alleles show enlarged aortae and underdeveloped cardinal veins, whereas those with loss-of-function mutations show small aortae and large cardinal veins. Notch does not affect the overall number of endothelial cells but balances the proportion of arterial to venous endothelial cells, thereby modulating the relative sizes of both vessel types. Loss of ephrin B2 or its receptor EphB4 also leads to enlarged aortae and underdeveloped cardinal veins; however, endothelial cells with venous identity are mislocalized in the aorta, suggesting that ephrin B2/EphB4 signaling functions distinctly from Notch by sorting arterial and venous endothelial cells into their respective vessels. Our findings provide mechanistic insight into the processes underlying artery and vein size equilibration during angiogenesis.

Key words: Angiogenesis, Vascular morphogenesis, Notch, Ephrin B2/EphB4, Mouse, Arterial-venous differentiation

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