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

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

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada (G.-H. Fong, J. Rossant, M. Gertsenstein, M. L. Breitman).
Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada (J. Rossant, M. L. Breitman)
(G.-H. Fong) Present address: The Lawson Research Institute, St Joseph's Health Center, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada.
(J. Rossant) To whom correspondence should be addressed.
(M. L. Breitman) Deceased.

Nature 376(6535):p 66-70, July 6, 1995.

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 vasculature . 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-1^lcz, 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-1^lcz 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.