Role of Egfl7 During Vascular Development

Abstract

Epidermal growth factor domain‐like 7, Egfl7, encodes a 29kDa protein with an early and endothelial‐restricted expression profile. In vivo, Egfl7 mRNA is detected at mouse embryonic day 7.5. During development, expression is restricted to sites of blood island formation, the vascular endothelium, and endocardium. In adults, Egfl7 is down‐regulated except in the lung, pregnant uterus, and regenerating endothelium. We have used loss‐ and gain‐of‐function to determine the role of Egfl7 during vasculogenesis and angiogenesis. We are using a lentiviral siRNA‐mediated approach to establish Egfl7 knock‐down in ESC clones and transgenic mice. Embryoid bodies with Egfl7 knock‐down appear to have less organized vascular cords compared with controls. Tie2‐Egfl7 transgenic mice, with forced expression of the gene in endothelial cells, have been generated for gain‐of‐function analysis, and these display increased vessel lumen diameter, hemorrhaging, and other vascular abnormalities. We will report on analyses of these ESC and transgenic mice studies, and describe how they relate to the role of Egfl7 during embryogenesis. In addition, we will report on a second site of Egfl7 expression in embryonic germ cells (EGC) and embryonic stem cells (ESC), primordial stem cells, and during adult spermatogenesis.Research Support: NIH HL082098, Tri‐Institutional Stem Cell Initiative (H.S.)