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Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium

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Abstract

THE vascular endothelial growth factor (VEGF) and its high-affinity binding receptors, the tyrosine kinases Flt-1 and Flk-1, are thought to be important for the development of embryonic vasculature1–8. Here we report that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation. Mouse embryos homozygous for a targeted mutation in the flt-1 locus, flt-llcz formed endothelial cells in both embryonic and extra-embryonic regions, but assembled these cells into abnormal vascular channels and died in utero at mid-somite stages. At earlier stages, the blood islands of flt-llcz homozygotes were abnormal, with angioblasts in the interior as well as on the periphery. We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development.

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Author notes

  1. Guo-Hua Fong

    Present address: The Lawson Research Institute, St Joseph's Health Centre, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada

  2. Martin L. Breitman: Deceased

Authors and Affiliations

  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Guo-Hua Fong, Janet Rossant, Marina Gertsenstein & Martin L. Breitman

  2. Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada

    Janet Rossant & Martin L. Breitman

Authors
  1. Guo-Hua Fong
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  2. Janet Rossant
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  3. Marina Gertsenstein
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  4. Martin L. Breitman
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Fong, GH., Rossant, J., Gertsenstein, M. et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376, 66–70 (1995). https://doi.org/10.1038/376066a0

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