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- W78450198 abstract "Blood vessel patterning during angiogenesis is a guided process. Endothelial tip cellslocated at the end of vascular sprouts are important for vessel guidance. One of theaims of my studies is to determine how endothelial tip cell formation is regulated.Previous studies have shown that the Notch ligand, Delta-like 4 (Dll4), isprominently expressed in tip cells, therefore suggesting a role of Notch signalling inits regulation. In the mouse, suppression of Notch signalling by pharmacologicalinhibition of γ-secretase or genetic deletion of one Dll4 allele resulted in excessiveendothelial tip cell formation and a poorly-patterned, hyperdense vessel network.Induction of Notch signalling by Jagged1 peptide treatment led to a decrease in tipcell formation and a sparse vessel network. Thus, the Notch pathway negativelyregulates tip cell formation to promote a non-sprouting endothelial stalk cell.The Notch-regulated ankyrin repeat protein, Nrarp, is a Notch target genethat is highly expressed in stalk cells and endothelial cells located at vesselbranchpoints. Deletion of Nrarp in mouse and morpholino knockdown of nrarp-aand nrarp-b in zebrafish resulted in decreased endothelial cell proliferation andjunctional instability, leading to ectopic vessel regression and the formation of asparse vessel network. In endothelial cells, loss of Nrarp function increased Notchsignalling but decreased Wnt signalling, thereby confirming its role as a negative andpositive modulator of Notch and Wnt signalling, respectively. Mice null forLymphoid enhancer factor 1 (Lef1) or deficient in endothelial Ctnnb1 also displayedincreased vessel regression and decreased vessel density, suggesting a role ofcanonical Wnt/β-catenin signalling in maintaining vessel stability.In conclusion, my studies show that Notch signalling regulates endothelial tipcell formation and vessel stability to fine-tune vessel patterning. Furthermore, Idemonstrate that Nrarp provides a molecular link to Wnt signalling to regulate vesselstability." @default.
- W78450198 created "2016-06-24" @default.
- W78450198 creator A5014861973 @default.
- W78450198 date "2009-01-28" @default.
- W78450198 modified "2023-09-24" @default.
- W78450198 title "A study of Notch signalling in developmental angiogenesis" @default.
- W78450198 hasPublicationYear "2009" @default.
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