EGFL7 in vascular development and repair

Abstract

Egfl7 is an EGF-domain gene expressed in developing blood vessels in mouse embryos, and during endothelial regeneration in adults. Our aim is to determine the role of Egfl7 in the formation and maintenance of blood vessels. Using in situ hybridisation and immunostaining we have found that Egfl7 is present in the inner cell mass at embryonic day 7.5, in the visceral yolk sac at sites of angioblast differentiation, and in the vascular endothelium and endocardium of the embryo proper. Furthermore, Egfl7 expression is down-regulated in adult organs with notable exceptions: lung, sites of vascular injury, and pregnant uterus. Our results indicate that EGFL7 is a secreted cell surface protein, and cell migration assays show that the protein is a chemoattractant for embryonic endothelial cells and fibroblasts. Preliminary work implies that EGFL7 interacts with endothelial Notch4, and may bind to extracellular matrix proteins. Together, these results strongly suggest that Egfl7 has an important role during development and regeneration of the vasculature, and that EGFL7-positive cells could potentially be target cells for future gene delivery studies into whole animals. We will report on continuing work using siRNA-mediated knock-down, GFP knock-in, and transgenic mouse lines. Funding provided by NIH grants; R21 HL072270, R01 HL082098 to H.S., in part by T32 HL07695 to M.J.F. and S.C., and AHA fellowship 0525046Y to A.D.