title: Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation.
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.
authors.affiliation: Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Shane P
authors.initials: SP
authors.lastname: Herbert
authors.forename: Jan
authors.initials: J
authors.lastname: Huisken
authors.forename: Tyson N
authors.initials: TN
authors.lastname: Kim
authors.forename: Morri E
authors.initials: ME
authors.lastname: Feldman
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Houseman
authors.forename: Rong A
authors.initials: RA
authors.lastname: Wang
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000166:cytology / Q000196:embryology; D001158:Arteries / Q000166:cytology / Q000196:embryology*; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D036388:Ephrin-B2 / Q000378:metabolism*; D009024:Morphogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D036224:Receptor, EphB4 / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D014680:Veins / Q000166:cytology / Q000196:embryology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D036388:Ephrin-B2; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; D019869:Phosphatidylinositol 3-Kinases; D036224:Receptor, EphB4; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3