ZFIN ID: ZDB-PUB-170718-3
Endothelial Notch signalling limits angiogenesis via control of artery formation
Hasan, S.S., Tsaryk, R., Lange, M., Wisniewski, L., Moore, J.C., Lawson, N.D., Wojciechowska, K., Schnittler, H., Siekmann, A.F.
Date: 2017
Source: Nature Cell Biology 19(8): 928-940 (Journal)
Registered Authors: Lawson, Nathan, Moore, John, Siekmann, Arndt Friedrich
Keywords: Angiogenesis, Cell migration, Zebrafish
MeSH Terms: none
PubMed: 28714969 Full text @ Nat. Cel. Biol.
ABSTRACT
Angiogenic sprouting needs to be tightly controlled. It has been suggested that the Notch ligand dll4 expressed in leading tip cells restricts angiogenesis by activating Notch signalling in trailing stalk cells. Here, we show using live imaging in zebrafish that activation of Notch signalling is rather required in tip cells. Notch activation initially triggers expression of the chemokine receptor cxcr4a. This allows for proper tip cell migration and connection to the pre-existing arterial circulation, ultimately establishing functional arterial-venous blood flow patterns. Subsequently, Notch signalling reduces cxcr4a expression, thereby preventing excessive blood vessel growth. Finally, we find that Notch signalling is dispensable for limiting blood vessel growth during venous plexus formation that does not generate arteries. Together, these findings link the role of Notch signalling in limiting angiogenesis to its role during artery formation and provide a framework for our understanding of the mechanisms underlying blood vessel network expansion and maturation.
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