ROLE OF THE FLT-1 RECEPTOR TYROSINE KINASE IN REGULATING THE ASSEMBLYOF VASCULAR ENDOTHELIUM

THE vascular endothelial growth factor (VEGF) and its high-affinity bi nding receptors, the tyrosine kinases Flt-1 and Flk-1, are thought to be important for the development of embryonic vasculature(1-8). Here w e report that Flt-1 is essential for the organization of embryonic vas culature, but is not essential for endothelial cell differentiation. M ouse embryos homozygous for a targeted mutation in the flt-1 locus, fl t-1(lcz), formed endothelial cells in both embryonic and extra-embryon ic regions, but assembled these cells into abnormal vascular channels and died in utero at mid-somite stages. At earlier stages, the blood i slands of flt-1(lcz) homozygotes were abnormal, with angioblasts in th e interior as well as on the periphery. We suggest that the Flt-1 sign alling pathway may regulate normal endothelial cell-cell or cell-matri x interactions during vascular development.