Liver organogenesis promoted by endothelial cells prior to vascular function

The embryonic role of endothelial cells and nascent vessels in promoting or ganogenesis, prior to vascular function, is unclear. We find that early end othelial cells in mouse embryos surround newly specified hepatic endoderm a nd delimit the mesenchymal domain into which the Liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed a n embryo tissue explant system that permits liver bud vasculogenesis and sh ow that in the absence of endothelial cells, or when the latter are inhibit ed, there is a selective defect in hepatic outgrowth. We conclude that vasc ulogenic endothelial cells and nascent vessels are critical for the earlies t stages of organogenesis, prior to blood vessel function.