Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish.

Abstract:

:Recent evidence indicates a specific role for vascular endothelial growth factor a (Vegfa) during artery development in both zebrafish and mouse embryos, whereas less is known about signals that govern vein formation. In zebrafish, loss of vegfa blocks segmental artery formation and reduces artery-specific gene expression, whereas veins are largely unaffected. Here, we describe a mutation in the zebrafish vegf receptor-2 homolog, kdra, which eliminates its kinase activity and leads to specific defects in artery development. We further find that Flt4, a receptor for Vegfc, cooperates with Kdr during artery morphogenesis, but not differentiation. We also identify an additional zebrafish vegfr-2 ortholog, referred to as kdrb, which can partially compensate for loss of kdra but is dispensable for vascular development in wild-type embryos. Interestingly, we find that these Vegf receptors are also required for formation of veins but in distinct genetic interactions that differ from those required for artery development. Taken together, our results indicate that formation of arteries and veins in the embryo is governed in part by different Vegf receptor combinations and suggest a genetic mechanism for generating blood vessel diversity during vertebrate development.

authors

Covassin LD,Villefranc JA,Kacergis MC,Weinstein BM,Lawson ND

doi

10.1073/pnas.0506886103

subject

Has Abstract

pub_date

2006-04-25 00:00:00

pages

6554-9

issue

17

eissn

0027-8424

issn

1091-6490

pii

0506886103

journal_volume

103

pub_type

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