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  Svep1 stabilises developmental vascular anastomosis in reduced flow conditions

Coxam, B., Collins, R. T., Hussmann, M., Huisman, Y., Meier, K., Jung, S., et al. (2022). Svep1 stabilises developmental vascular anastomosis in reduced flow conditions. DEVELOPMENT, 149(6): dev199858. doi:10.1242/dev.199858.

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 Creators:
Coxam, Baptiste, Author
Collins, Russell T., Author
Hussmann, Melina, Author
Huisman, Yvonne, Author
Meier, Katja, Author
Jung, Simone, Author
Bartels-Klein, Eireen, Author
Szymborska, Anna, Author
Finotto, Lise, Author
Helker, Christian S. M.1, Author              
Stainier, Didier Y. R.1, Author              
Schulte-Merker, Stefan, Author
Gerhardt, Holger, Author
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              

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 Abstract: Molecular mechanisms controlling the formation, stabilisation 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 klf2a. Experimentally, further increasing Vegfa/Vegfr signalling can rescue the DLAV formation and lumenisation defects, whereas its inhibition dramatically exacerbates the loss of connectivity. Mechanistically, our results suggest that flow and Svep1 co-regulate the stabilisation of vascular connections, in part by modulating the Vegfa/Vegfr signalling pathway.

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 Dates: 2022-03-24
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000777475500014
DOI: 10.1242/dev.199858
PMID: 35312765
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Title: DEVELOPMENT
Source Genre: Journal
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Pages: - Volume / Issue: 149 (6) Sequence Number: dev199858 Start / End Page: - Identifier: ISSN: 0950-1991