The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling


  • G.M. Birdsey
  • A.V. Shah
  • N. Dufton
  • L.E. Reynolds
  • L. Osuna Almagro
  • Y. Yang
  • I.M. Aspalter
  • S.T. Khan
  • J.C. Mason
  • E. Dejana
  • B. Göttgens
  • K. Hodivala-Dilke
  • H. Gerhardt
  • R.H. Adams
  • A.M. Randi


  • Developmental Cell


  • Dev Cell 32 (1): 82-96


  • Blood vessel stability is essential for embryonic development; in the adult, many diseases are associated with loss of vascular integrity. The ETS transcription factor ERG drives expression of VE-cadherin and controls junctional integrity. We show that constitutive endothelial deletion of ERG (Erg(cEC-KO)) in mice causes embryonic lethality with vascular defects. Inducible endothelial deletion of ERG (Erg(iEC-KO)) results in defective physiological and pathological angiogenesis in the postnatal retina and tumors, with decreased vascular stability. ERG controls the Wnt/{beta}-catenin pathway by promoting {beta}-catenin stability, through signals mediated by VE-cadherin and the Wnt receptor Frizzled-4. Wnt signaling is decreased in ERG-deficient endothelial cells; activation of Wnt signaling with lithium chloride, which stabilizes {beta}-catenin levels, corrects vascular defects in Erg(cEC-KO) embryos. Finally, overexpression of ERG in vivo reduces permeability and increases stability of VEGF-induced blood vessels. These data demonstrate that ERG is an essential regulator of angiogenesis and vascular stability through Wnt signaling.