title: Stepwise arteriovenous fate acquisition during mammalian vasculogenesis.
abstract: Arteriovenous (AV) differentiation is a critical step during blood vessel formation and stabilization. Defects in arterial or venous fate lead to inappropriate fusion of vessels, resulting in damaging arteriovenous shunts. While many studies have unraveled the molecular underpinnings that drive AV fate, surprisingly, the spatiotemporal emergence of arteries and veins in mammalian embryos remains unknown. Here, we examine artery and vein specification and differentiation during vasculogenesis. We show that the first intraembryonic vessels formed are arteries, which differentiate in a stepwise manner. By contrast, veins emerge later, progressively forming after embryonic turning. In addition, we demonstrate that hemodynamic flow is not required for arterial specification, but is required for maintenance of select arterial markers. Together, our results provide a first spatiotemporal analysis of mammalian AV cell fate establishment and anatomy, as well as a delineation of a molecular toolkit for analysis of arteries and veins during early vessel development.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Chong
authors.forename: Yeon
authors.initials: Y
authors.lastname: Koo
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Stephen
authors.initials: S
authors.lastname: Fu
authors.forename: Ondine
authors.initials: O
authors.lastname: Cleaver
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001158:Arteries / Q000196:embryology*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006439:Hemodynamics / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D014680:Veins / Q000196:embryology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins