title: The role of extracellular matrix in vascular branching morphogenesis.
abstract: Angiogenesis requires the development of a hierarchically branched network of vessels, which undergoes radial expansion and anastomosis to form a close circuit. Branching is achieved by coordinated behavior of endothelial cells that organize into leading "tip" cells and trailing "stalk" cells. Such organization is under control of the Dll4-Notch signaling pathway, which sets a hierarchy in receptiveness of cells to VEGF-A. Recent studies have shed light on a control of the Notch pathway by basement membrane proteins and integrin signaling, disclosing that extracellular matrix exerts active control on vascular branching morphogenesis. We will survey in the present review how extracellular matrix is a multifaceted substrate, which behind a classical structural role hides a powerful conductor function to shape the branching pattern of vessels.
authors.affiliation: INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Université de Nice-Sophia-Antipolis, Nice, France. amel.mettouchi@unice.fr
authors.forename: Amel
authors.initials: A
authors.lastname: Mettouchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D010766:Phosphorylation; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D012171:Retinal Vessels / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D005353:Fibronectins; D039001:Integrin alpha Chains; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2