Svep1 stabilises developmental vascular anastomosis in reduced flow conditions.
Development
; 149(6)2022 03 15.
Article
em En
| MEDLINE
| ID: mdl-35312765
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Proteínas de Peixe-Zebra
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article