Development of the intrahepatic biliary tree.

The liver develops from two anlages: the hepatic diverticulum, which buds off the ventral side of the foregut, and the septum transversum, which is the mesenchymal plate that partially separates the embryonic thoracic and abdominal cavities. The endodermal cells of the hepatic diverticulum invade the septum transversum, forming sheets and cords of hepatoblasts arrayed along the sinusoidal vascular channels derived from the vitelline veins emanating from the yolk sac. The vitelline veins fuse to form the portal vein, which ramifies as tributaries within the liver along mesenchymal channels termed portal tracts. Those hepatoblasts immediately adjacent to the mesenchyme of the portal tracts differentiate into a ductal plate, a single circumferential layer of biliary epithelial cells. Mesenchymal cells interpose between the ductal plate and the remaining parenchymal hepatoblasts, which differentiate into hepatocytes. By week 7 the ductal plate begins to reduplicate, forming a double layer of cells around the portal tract. Lumena form between the two cell layers of the ductal plate, forming peripheral biliary tubular structures. These peripheral tubules remodel and, with continued proliferation of the mesenchyme, by the 11th week begin to become more centrally located within portal tracts as terminal bile ducts with a circular cross-section. The remaining ductal plate resorbs, leaving behind only tethers of bile ductules connecting the terminal bile ducts to the parenchyma. Abutting and within the parenchyma are the canals of Hering, ductular structures half-lined by hepatocytes and half-lined by biliary epithelial cells. Maturation of the intrahepatic biliary tree to the mature tubular treelike architecture occurs from the hilum of the liver outward, beginning around the 11th week of gestation and continuing past birth for several months. The architecture of maturation is the same regardless of gestational age or radial location in the liver. Importantly, the immature intrahepatic biliary system maintains patency and continuity with the extrahepatic biliary tree throughout gestation, with no evidence of a solid phase of development. Thus, from the earliest time of hepatocellular bile formation beginning around the 12th week, there is a patent passage to the alimentary canal.