Molecular mechanisms controlling the formation, stabilization and maintenance of blood vessel connections remain poorly defined. Here we identify blood flow and the large extracellular protein Svep1 as co-modulators of vessel anastomosis during developmental angiogenesis in zebrafish embryos. Both loss of Svep1 and blood flow reduction contribute to defective anastomosis of intersegmental vessels. The reduced formation and lumenisation of the dorsal longitudinal anastomotic vessel (DLAV) is associated with a compensatory increase in Vegfa/Vegfr pERK signalling, concomittant expansion of apelin-positive tip cells, but reduced expression of klf2. Experimentally, further increasing Vegfa/Vegfr signalling can rescue the DLAV formation and lumenisation defects, while its inhibition dramatically exacerbates the loss of connectivity. Mechanistically, our results suggest that flow and Svep1 co-regulate the stabilization of vascular connections, in part by modulating the Vegfa/Vegfr signalling pathway.
Svep1 stabilizes developmental vascular anastomosis in reduced flow conditions
Present address: Philipps-University Marburg, Faculty of Biology, Cell Signaling and Dynamics, Marburg, 35043, Germany
- Award Group:
- Funder(s): Fondation Leducq
- Award Id(s): 17 CVD 03
- Funder(s):
- Award Group:
- Funder(s): Deutsche Forschungsgemeinschaft
- Award Id(s): CRC1348
- Funder(s):
- Award Group:
- Funder(s): Deutsches Zentrum fur Herz-Kreislaufforschung
- Award Id(s): EX2-B DR_Coxam
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
Baptiste Coxam, Russell T. Collins, Melina Hußmann, Yvonne Huisman, Katja Meier, Simone Jung, Eireen Bartels-Klein, Anna Szymborska, Lise Finotto, Christian S.M. Helker, Didier Y.R. Stainier, Stefan Schulte-Merker, Holger Gerhardt; Svep1 stabilizes developmental vascular anastomosis in reduced flow conditions. Development 2022; dev.199858. doi: https://doi.org/10.1242/dev.199858
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