title: Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting.
abstract: Many studies reveal a fundamental role for extracellular matrix-mediated signaling through integrins and Rho GTPases as well as matrix metalloproteinases (MMPs) in the molecular control of vascular tube morphogenesis in three-dimensional (3D) tissue environments. Recent work has defined an endothelial cell (EC) lumen signaling complex of proteins that controls these vascular morphogenic events. These findings reveal a signaling interdependence between Cdc42 and MT1-MMP to control the 3D matrix-specific process of EC tubulogenesis. The EC tube formation process results in the creation of a network of proteolytically generated vascular guidance tunnels in 3D matrices that are utilized to remodel EC-lined tubes through EC motility and could facilitate processes such as flow-induced remodeling and arteriovenous EC sorting and differentiation. Within vascular guidance tunnels, key dynamic interactions occur between ECs and pericytes to affect vessel remodeling, diameter, and vascular basement membrane matrix assembly, a fundamental process necessary for endothelial tube maturation and stabilization. Thus, the EC lumen and tube formation mechanism coordinates the concomitant establishment of a network of vascular tubes within tunnel spaces to allow for flow responsiveness, EC-mural cell interactions, and vascular extracellular matrix assembly to control the development of the functional microcirculation.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Davis
authors.forename: Amber N
authors.initials: AN
authors.lastname: Stratman
authors.forename: Anastasia
authors.initials: A
authors.lastname: Sacharidou
authors.forename: Wonshill
authors.initials: W
authors.lastname: Koh
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D016764:Cell Polarity; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D053511:Matrix Metalloproteinase 14; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009024:Morphogenesis; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D019061:src-Family Kinases; D051744:Protein Kinase C-epsilon; D020782:Matrix Metalloproteinases; D053511:Matrix Metalloproteinase 14; D020764:cdc42 GTP-Binding Protein