title: Robustness in angiogenesis: notch and BMP shaping waves.
abstract: Vascular patterning involves sprouting of blood vessels, which is governed by orchestrated communication between cells in the surrounding tissue and endothelial cells (ECs) lining the blood vessels. Single ECs are selected for sprouting by hypoxia-induced stimuli and become the 'tip' or leader cell that guides new sprouts. The 'stalk' or trailing ECs proliferate for tube extension and lumenize the nascent vessel. Stalk and tip cells can dynamically switch their identities during this process in a Notch-dependent manner. Here, we review recent studies showing that bone morphogenetic protein (BMP) signaling coregulates Notch target genes in ECs. In particular, we focus on how Delta-like ligand 4 (DLL4)-Notch and BMP effector interplay may drive nonsynchronized oscillatory gene expression in ECs essential for setting sharp tip-stalk cell boundaries while sustaining a dynamic pool of nonsprouting ECs. Deeper knowledge about the coregulation of vessel plasticity in different vascular beds may result in refinement of anti-angiogenesis and vessel normalization therapies.
authors.affiliation: Laboratory of Developmental Signaling, VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Beets
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
authors.forename: Iván M
authors.initials: IM
authors.lastname: Moya
authors.forename: Lieve
authors.initials: L
authors.lastname: Umans
authors.forename: An
authors.initials: A
authors.lastname: Zwijsen
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001808:Blood Vessels / Q000254:growth & development / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch; D051785:Smad Proteins