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Science 326 (5950): 294-298

Copyright © 2009 by the American Association for the Advancement of Science

Arterial-Venous Segregation by Selective Cell Sprouting: An Alternative Mode of Blood Vessel Formation

Shane P. Herbert,1,2 Jan Huisken,1 Tyson N. Kim,3 Morri E. Feldman,4 Benjamin T. Houseman,5 Rong A. Wang,3 Kevan M. Shokat,5 Didier Y. R. Stainier1,*

Abstract: Blood vessels form de novo (vasculogenesis) or upon sprouting of capillaries from preexisting vessels (angiogenesis). With high-resolution imaging of zebrafish vascular development, we uncovered a third mode of blood vessel formation whereby the first embryonic artery and vein, two unconnected blood vessels, arise from a common precursor vessel. The first embryonic vein formed by selective sprouting of progenitor cells from the precursor vessel, followed by vessel segregation. These processes were regulated by the ligand EphrinB2 and its receptor EphB4, which are expressed in arterial-fated and venous-fated progenitors, respectively, and interact to orient the direction of progenitor migration. Thus, directional control of progenitor migration drives arterial-venous segregation and generation of separate parallel vessels from a single precursor vessel, a process essential for vascular development.

1 Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.
2 Multidisciplinary Cardiovascular Research Centre and Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
3 Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.
4 Graduate Group in Biophysics, University of California, San Francisco, CA 94158, USA.
5 Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: Didier.Stainier{at}

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