Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression

L. Miquerol, B. L. Langille, A. Nagy

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330 Citations (Scopus)

Abstract

Previous work has shown that heterozygocity for a null mutation of the VEGF-A gene, resulting in a 50% reduction in VEGF-A expression, is embryonic lethal at embroyonic day (E) 9.5 in mice. We now show that two- to threefold overexpression of VEGF-A from its endogenous locus results in severe abnormalities in heart development and embryonic lethality at E12.5-E14. The mutant embryos displayed an attenuated compact layer of myocardium, overproduction of trabeculae, defective ventricular septation and abnormalities in remodeling of the outflow track of the heart. In addition, aberrant coronary development was characterized by formation of oversized epicardial vessels, apparently through vasculogenesis. We infer that embryonic survival requires a narrow window of VEGF-A expression.

Original languageEnglish
Pages (from-to)3941-3946
Number of pages6
JournalDevelopment
Volume127
Issue number18
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Cardiogenesis
  • Coronary development
  • Gene regulation
  • Mouse
  • Septation
  • Vascular endothelial growth factor

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