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

Student Author(s)

Jacques A. Villefranc

Academic Program

Interdisciplinary Graduate Program

UMMS Affiliation

Program in Gene Function and Expression

Publication Date


Document Type



Cell and Developmental Biology | Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6554-9. Epub 2006 Apr 14. Link to article on publisher's site

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to article in PubMed

PubMed ID