Svep1 stabilises developmental vascular anastomosis in reduced flow conditions
| Item Type: | Article |
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| Title: | Svep1 stabilises developmental vascular anastomosis in reduced flow conditions |
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| Creators Name: | Coxam, B. and Collins, R.T. and Hußmann, M. and Huisman, Y. and Meier, K. and Jung, S. and Bartels-Klein, E. and Szymborska, A. and Finotto, L. and Helker, C.S.M. and Stainier, D.Y.R. and Schulte-Merker, S. and Gerhardt, H. |
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| Abstract: | 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. |
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| Keywords: | Anastomosis, Angiogenesis, Development, Vegfa/Vegfr Signalling, Animals, Zebrafish |
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| Source: | Development |
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| ISSN: | 0950-1991 |
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| Publisher: | Company of Biologists |
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| Volume: | 149 |
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| Number: | 6 |
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| Page Range: | dev199858 |
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| Date: | 24 March 2022 |
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| Official Publication: | https://doi.org/10.1242/dev.199858 |
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| PubMed: | View item in PubMed |
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| Related to: | |
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