Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression
L Miquerol, BL Langille, A Nagy - Development, 2000 - journals.biologists.com
L Miquerol, BL Langille, A Nagy
Development, 2000•journals.biologists.comPrevious 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 …
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 …
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.
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