Multiple developmental roles of VEGF suggested by a LacZ-tagged allele

Lucile Miquerol, Marina Gertsenstein, Kendraprasad Harpal, Janet Rossant, Andras Nagy

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Vascular endothelial growth factor (VEGF) is an angiogenic factor and a potent stimulator of microvascular permeability. It is a mitogen specific for endothelial cells. The expression of VEGF and its two receptors, Flk-1 and Flt-1, is pivotal for the proper formation of blood vessels in embryogenesis as shown by gene-targeting experiments. Interestingly, the loss of even a single allele of VEGF led to embryonic lethality between day E9.5 and day E10.5 in the mouse. To assess the role of VEGF during embryonic development we decided to tag VEGF expression with LacZ, by inserting an IRES (internal ribosome entry site)-LacZ reporter cassette into the 3' untranslated region of the gene. This alteration enabled us to monitor VEGF expression throughout embryonic development at single-cell resolution, β-Galactosidase expression from the altered VEGF locus was first observed prior to gastrulation and was detectable at all stages of vascular development in the embryo. Later, the specific cellular distribution and the level of VEGF expression indicated its pleiotropic role in development. High expression levels seemed to be associated with vasculogenesis and permeability, whereas lower levels were associated with angiogenesis and cell migration. In addition, we found VEGF expression in a subtype of endothelial cells present in the endocardium. We believe that the LacZ-tagged allele we have generated offers a precise means of detecting VEGF expression under a variety of physiological and pathological conditions.

Original languageEnglish
Pages (from-to)307-322
Number of pages16
JournalDevelopmental Biology
Issue number2
Publication statusPublished - 15 Aug 1999
Externally publishedYes


  • Angiogenesis
  • Embryonic development
  • Endothelial cells
  • Gene targeting
  • IRES-lacZ knock-in
  • Vascular endothelial growth factor
  • Vasculogenesis

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