title: Notch promotes vascular maturation by inducing integrin-mediated smooth muscle cell adhesion to the endothelial basement membrane.
abstract: Vascular development and angiogenesis initially depend on endothelial tip cell invasion, which is followed by a series of maturation steps, including lumen formation and recruitment of perivascular cells. Notch ligands expressed on the endothelium and their cognate receptors expressed on perivascular cells are involved in blood vessel maturation, though little is known regarding the Notch-dependent effectors that facilitate perivascular coverage of nascent vessels. Here, we report that vascular smooth muscle cell (VSMC) recognition of the Notch ligand Jagged1 on endothelial cells leads to expression of integrin αvβ3 on VSMCs. Once expressed, integrin αvβ3 facilitates VSMC adhesion to VWF in the endothelial basement membrane of developing retinal arteries, leading to vessel maturation. Genetic or pharmacologic disruption of Jagged1, Notch, αvβ3, or VWF suppresses VSMC coverage of nascent vessels and arterial maturation during vascular development. Therefore, we define a Notch-mediated interaction between the developing endothelium and VSMCs leading to adhesion of VSMCs to the endothelial basement membrane and arterial maturation.
authors: Department of Pathology and Moores UCSD Cancer Center, University of California-San Diego, La Jolla, CA, USA.
authors: Lea
authors: L
authors: Scheppke
authors: Eric A
authors: EA
authors: Murphy
authors: Alessandro
authors: A
authors: Zarpellon
authors: Jennifer J
authors: JJ
authors: Hofmann
authors: Alona
authors: A
authors: Merkulova
authors: David J
authors: DJ
authors: Shields
authors: Sara M
authors: SM
authors: Weis
authors: Tatiana V
authors: TV
authors: Byzova
authors: Zaverio M
authors: ZM
authors: Ruggeri
authors: M Luisa
authors: ML
authors: Iruela-Arispe
authors: David A
authors: DA
authors: Cheresh
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D014841:von Willebrand Factor