Defective development of the embryonic liver in N-myc-deficient mice.

The mechanisms involved in the formation and the differentiation of the liver remain unclear despite extensive studies. To investigate these events in mouse hepatic development, we have taken advantage of the N-myc mutant mouse line which exhibits abnormal liver development. N-myc mutant embryos die between 11.5 and 12.5 days postcoitum most probably from heart failure. In the present study, we report that at 11.5 days of gestation, extensive apoptosis restricted to the hepatocytes occurred in N-myc mutant liver when compared to wild-type samples. Moreover, the number of hematopoietic cells is reduced in the mutant liver. During early liver organogenesis, the N-myc gene is expressed in tissues involved in the induction and the differentiation of the hepatocytes. At 11.5 days postcoitum, both c-myc and N-myc genes are expressed in the liver. While c-myc is expressed at a high level in the organ per se, N-myc expression is mostly confined to the peripheral layer of the liver which will generate the Glisson's capsule. Taken together, the expression pattern of N-myc in the liver and the specific apoptosis of hepatocytes observed in N-myc mutants indicate that N-myc is required for hepatocyte survival and suggest that it is involved in the genetic cascade leading to normal liver development.