Fong G H, Rossant J, Gertsenstein M, Breitman M L
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Nature. 1995 Jul 6;376(6535):66-70. doi: 10.1038/376066a0.
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.
血管内皮生长因子（VEGF）及其高亲和力结合受体——酪氨酸激酶Flt-1和Flk-1，被认为对胚胎血管系统的发育至关重要。在此我们报告，Flt-1对胚胎血管系统的组织形成必不可少，但对内皮细胞分化并非必不可少。flt-1基因座发生靶向突变的纯合小鼠胚胎flt-1lcz，在胚胎和胚外区域均形成了内皮细胞，但这些细胞组装成了异常的血管通道，并在中体节阶段死于子宫内。在更早的阶段，flt-1lcz纯合子的血岛异常，内部和周边都有成血管细胞。我们认为，Flt-1信号通路可能在血管发育过程中调节正常的内皮细胞-细胞或细胞-基质相互作用。
