Hedgehog regulates angiogenesis of intersegmental vessels through the VEGF signaling pathway

Carlos M. Moran, Candace T. Myers, Cristy M. Lewis, Paul A. Krieg

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1034-1042
Number of pages9
JournalDevelopmental Dynamics
Volume241
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Cyclopamine
  • DAPT
  • DLL4
  • Endothelial development
  • Hedgehog
  • ISV
  • SAG
  • Smoothened agonist

ASJC Scopus subject areas

  • Developmental Biology

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