Defective Vascular Morphogenesis and Mid-Gestation Embryonic Death in Mice Lacking RA-GEF-1

Biochem Biophys Res Commun. 2007 Nov 9;363(1):106-12. doi: 10.1016/j.bbrc.2007.08.149. Epub 2007 Sep 10.


A multitude of guanine nucleotide exchange factors (GEFs) regulate Rap1 small GTPases, however, their individual functions remain obscure. Here, we investigate the in vivo function of the Rap1 GEF RA-GEF-1. The expression of RA-GEF-1 in wild-type mice starts at embryonic day (E) 8.5, and continues thereafter. RA-GEF-1(-/-) mice appear normal until E7.5, but become grossly abnormal and dead by E9.5. This mid-gestation death appears to be closely associated with severe defects in yolk sac blood vessel formation. RA-GEF-1(-/-) yolk sacs form apparently normal blood islands by E8.5, but the blood islands fail to coalesce into a primary vascular plexus, indicating that vasculogenesis is impaired. Furthermore, RA-GEF-1(-/-) embryos proper show severe defects in the formation of major blood vessels. These results suggest that deficient Rap1 signaling may lead to defective vascular morphogenesis in the yolk sac and embryos proper.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / abnormalities*
  • Blood Vessels / metabolism*
  • Embryo Loss / metabolism*
  • Female
  • Gene Silencing
  • Gestational Age
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphogenesis*
  • Neovascularization, Pathologic / embryology*
  • Neovascularization, Pathologic / metabolism*


  • CNrasGEF protein, mouse
  • Guanine Nucleotide Exchange Factors