title: Distinct Notch signaling outputs pattern the developing arterial system.
abstract: Differentiation of arteries and veins is essential for the development of a functional circulatory system. In vertebrate embryos, genetic manipulation of Notch signaling has demonstrated the importance of this pathway in driving artery endothelial cell differentiation. However, when and where Notch activation occurs to affect endothelial cell fate is less clear. Using transgenic zebrafish bearing a Notch-responsive reporter, we demonstrate that Notch is activated in endothelial progenitors during vasculogenesis prior to blood vessel morphogenesis and is maintained in arterial endothelial cells throughout larval stages. Furthermore, we find that endothelial progenitors in which Notch is activated are committed to a dorsal aorta fate. Interestingly, some arterial endothelial cells subsequently downregulate Notch signaling and then contribute to veins during vascular remodeling. Lineage analysis, together with perturbation of both Notch receptor and ligand function, further suggests several distinct developmental windows in which Notch signaling acts to promote artery commitment and maintenance. Together, these findings demonstrate that Notch acts in distinct contexts to initiate and maintain artery identity during embryogenesis.
authors.affiliation: Program in Gene Function and Expression, UMass Medical School, Worcester, MA 01605 USA.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Quillien
authors.forename: John C
authors.initials: JC
authors.lastname: Moore
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shin
authors.forename: Arndt F
authors.initials: AF
authors.lastname: Siekmann
authors.forename: Tom
authors.initials: T
authors.lastname: Smith
authors.forename: Luyuan
authors.initials: L
authors.lastname: Pan
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parsons
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000166:cytology / Q000196:embryology*; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D004625:Embryo, Nonmammalian; D004730:Endothelium, Vascular / Q000196:embryology; D009024:Morphogenesis / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014680:Veins / Q000196:embryology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D051880:Receptors, Notch
keywords: Artery differentiation; Notch; Vascular system; Zebrafish