Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function

TLDR

The role of endothelial cells and nascent vessels in early organogenesis before vascular function is unclear. An embryo tissue explant system demonstrated that endothelial cells are required for hepatic outgrowth, as their absence or inhibition causes selective defects. Early endothelial cells surround hepatic endoderm and delimit the mesenchymal domain, and their loss leads to failed liver morphogenesis before mesenchyme invasion, proving that vasculogenic endothelial cells are essential for the earliest stages of organogenesis prior to blood vessel function.

Abstract

The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and 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 an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.