Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse.

Differentiation of the endodermal cells of the mouse liver was studied enzymo- and immunocytochemically by analyzing the cellular localization of alphafoetoprotein (AFP), glycogen, and alkaline phosphatase (ALP) and 5'-nucleotidase (5'-Nase) activities. 1. In 8.5-day foetuses, AFP appears in some endodermal cells of the anterior intestinal portal region. The cells of the cranial diverticulum contain much AFP at 9.5 days, while those of the caudal diverticulum contain less AFP. 2. In 9.5- to 15.5-day foetuses, hepatocytes are intensely fluorescent for AFP. After 16.5 days less-positive hepatocytes increase in number. AFP is still present in a few hepatocytes of 14-day-old postnatal mice. ALP and 5'-Nase activities appear in a small proportion of hepatocytes at 13.5 and 14.5 days of embryonal life, respectively. At 15.5 days, many hepatocytes possess these enzyme activities, and initiate accumulation of glycogen. AFP-containing hepatocytes type I (gestation day 9.5-16.5) successively acquire ALP and 5'-Nase activities and accumulate glycogen, and then differentiate into hepatocytes type II after gestation day 17.5. 3. Endodermal cells constituting lumen structures in the liver trabeculae are the precursor of the intrahepatic bile duct cells. They possess much AFP, but no glycogen and no ALP activity, and are similar to hepatocytes type I. Since immature hepatic duct cells also possess much AFP, but no glycogen, and no ALP and 5'-Nase activities, they are similar to endodermal cells of the lumen structures. Therefore, that the endodermal cells of the lumen structures are the intermediate cells between hepatocytes type I and hepatic duct cells may be conceivable.