title: Notch controls retinal blood vessel maturation and quiescence.
abstract: Blood vessels form a hierarchically organized network of arteries, capillaries and veins, which develops through a series of growth, pruning and maturation processes. In contrast to the rapidly increasing insight into the processes controlling vascular growth and, in particular, endothelial sprouting and proliferation, the conversion of immature vessels into a fully functional, quiescent vasculature remains little understood. Here we used inducible, cell type-specific genetic approaches to show that endothelial Notch signaling is crucial for the remodeling of veins and the perivenous capillary plexus, which occurs after the completion of the initial angiogenic growth phase in the retina of adolescent mice. Mutant vessels showed ectopic proliferation and sprouting, defective recruitment of supporting mural cells, and failed to downregulate the expression of VEGF receptors. Surprisingly, by contrast Notch was dispensable in the endothelium of remodeling postnatal arteries. Taken together, our results identify key processes contributing to vessel remodeling, maturation and the acquisition of a quiescent phenotype in the final stage of developmental angiogenesis.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ehling
authors.forename: Susanne
authors.initials: S
authors.lastname: Adams
authors.forename: Rui
authors.initials: R
authors.lastname: Benedito
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D018390:Gene Targeting; D051379:Mice; D018919:Neovascularization, Physiologic; D051880:Receptors, Notch / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D012161:Retinal Artery / Q000166:cytology; D012171:Retinal Vessels / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051880:Receptors, Notch; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Angiogenesis; Endothelial cells; Mouse; Notch; Vascular development