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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 sproutingof capillaries from preexisting vessels (angiogenesis). Withhigh-resolution imaging of zebrafish vascular development, weuncovered a third mode of blood vessel formation whereby thefirst embryonic artery and vein, two unconnected blood vessels,arise from a common precursor vessel. The first embryonic veinformed by selective sprouting of progenitor cells from the precursorvessel, followed by vessel segregation. These processes wereregulated by the ligand EphrinB2 and its receptor EphB4, whichare expressed in arterial-fated and venous-fated progenitors,respectively, and interact to orient the direction of progenitormigration. Thus, directional control of progenitor migrationdrives arterial-venous segregation and generation of separateparallel vessels from a single precursor vessel, a process essentialfor 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}ucsf.edu
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