Role of the Flt-1 Receptor Tyrosine Kinase in Regulating the Assembly of Vascular Endothelium

Nature. 1995 Jul 6;376(6535):66-70. doi: 10.1038/376066a0.

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 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-1lcz, 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-1lcz 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • DNA Primers
  • Embryo, Mammalian / blood supply
  • Endothelial Growth Factors / physiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / embryology*
  • Heterozygote
  • Homozygote
  • Humans
  • Lymphokines / physiology
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Stem Cells
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors

Substances

  • DNA Primers
  • Endothelial Growth Factors
  • Lymphokines
  • Proto-Oncogene Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-1