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Hedgehog regulates angiogenesis of intersegmental vessels through the VEGF signaling pathway
Author(s) -
Moran Carlos M.,
Myers Candace T.,
Lewis Cristy M.,
Krieg Paul A.
Publication year - 2012
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23795
Subject(s) - cyclopamine , biology , angiogenesis , hedgehog , notch signaling pathway , hedgehog signaling pathway , microbiology and biotechnology , regulator , vascular endothelial growth factor , signal transduction , fibroblast growth factor , embryo , endocrinology , medicine , cancer research , vegf receptors , genetics , gene , receptor
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. Developmental Dynamics 241:1034–1042, 2012. © 2012 Wiley Periodicals, Inc.