Hedgehog regulates angiogenesis of intersegmental vessels through the VEGF signaling pathway

Dev Dyn. 2012 Jun;241(6):1034-42. doi: 10.1002/dvdy.23795. Epub 2012 May 2.


Background: The cellular mechanisms regulating branching and growth of the intersegmental vessels (ISVs) are not well understood. We have carried out studies demonstrating that Hedgehog (Hh) signaling is a major regulator of intersomitic vessel growth.

Results: Inhibition of Hh activity by cyclopamine completely blocks formation of intersomitic vessels in the avian embryo. Examination of gene expression patterns in Hh-deficient embryos shows that components of the VEGF and Notch signaling pathways are down-regulated. However, we find no evidence that Notch signaling plays a significant role in regulation of intersomitic vessel growth. Indeed, it appears that Hh modulation of Vascular Endothelial Growth Factor, VEGF, is the primary regulator of growth of intersomitic vessels in the avian embryo.

Conclusions: Inhibition of the VEGF pathway results in absence of ISVs, whereas stimulation of VEGF expression leads to precocious branching of ISVs. These results demonstrate that Hh is an essential modulator of VEGF expression during developmental angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • DNA Primers / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Hedgehog Proteins / deficiency
  • Hedgehog Proteins / metabolism*
  • In Situ Hybridization
  • Neovascularization, Physiologic / physiology*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Somites / blood supply*
  • Vascular Endothelial Growth Factor A / metabolism*
  • Veratrum Alkaloids


  • DNA Primers
  • Hedgehog Proteins
  • Vascular Endothelial Growth Factor A
  • Veratrum Alkaloids
  • cyclopamine