Fig. 1.

Embryonic development of the intrahepatic biliary system. (A,B) At circa embryonic day (E) 8.25 in mouse, cells in the ventral foregut endoderm and ventral midline endodermal lip (VMEL) arise and contribute to the developing liver bud. (C) Next, the liver bud grows to engulf the vitelline veins, which form a vascular plexus that gives rise to hepatic sinusoids. The umbilical veins and cardinal veins also contribute to hepatic sinusoid formation. Portions of the vitelline veins anastomose and establish the portal vein – the scaffold for biliary system formation. (D) Portal vein mesenchyme surrounding the portal veins induces formation of the ductal plate, a layer of cholangiocytes surrounding the portal vein, in a process that initiates near the hilum and progresses towards the periphery. Small lumina form, with cholangiocytes on the portal side and hepatoblast-like cells on the parenchymal side that subsequently differentiate into cholangiocytes. In mice, bile ducts then induce formation of the hepatic artery, while in humans the inductive signal is thought to come from the ductal plate itself.