Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7 Academic Article uri icon


MeSH Major

  • Endothelium, Vascular
  • Hemorrhage
  • Neovascularization, Pathologic
  • Proteins
  • Receptors, Notch
  • Umbilical Veins


  • Epidermal growth factor-like domain 7 (Egfl7) is important for regulating tubulogenesis in zebrafish, but its role in mammals remains unresolved. We show here that endothelial overexpression of Egfl7 in transgenic mice leads to partial lethality, hemorrhaging, and altered cardiac morphogenesis. These defects are accompanied by abnormal vascular patterning and remodeling in both the embryonic and postnatal vasculature. Egfl7 overexpression in the neonatal retina results in a hyperangiogenic response, and EGFL7 knockdown in human primary endothelial cells suppresses endothelial cell proliferation, sprouting, and migration. These phenotypes are reminiscent of Notch inhibition. In addition, our results show that EGFL7 and endothelial-specific NOTCH physically interact in vivo and strongly suggest that Egfl7 antagonizes Notch in both the postnatal retina and in primary endothelial cells. Specifically, Egfl7 inhibits Notch reporter activity and down-regulates the level of Notch target genes when overexpressed. In conclusion, we have uncovered a critical role for Egfl7 in vascular development and have shown that some of these functions are mediated through modulation of Notch signaling.

publication date

  • December 23, 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC3031397

Digital Object Identifier (DOI)

  • 10.1182/blood-2010-03-274860

PubMed ID

  • 20947685

Additional Document Info

start page

  • 6133

end page

  • 43


  • 116


  • 26