DEFECTIVE DEVELOPMENT OF THE EMBRYONIC LIVER IN N-MYC-DEFICIENT MICE

The mechanisms involved in the formation and the differentiation of th e 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-my c mutant embryos die between 11.5 and 12.5 days postcoitum most probab ly from heart failure. In the present study, we report that at 11.5 da ys of gestation, extensive apoptosis restricted to the hepatocytes occ urred in N-myc mutant liver when compared to wild-type samples, Moreov er, the number of hematopoietic cells is reduced in the mutant liver. During early liver organogenesis, the N-myc gene is expressed in tissu es involved in the induction and the differentiation of the hepatocyte s. At 11.5 days postcoitum, both c-myc and N-myc genes are expressed i n 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 th e liver which will generate the Glisson's capsule. Taken together, the expression pattern of N-myc in the liver and the specific apoptosis o f hepatocytes observed in N-myc mutants indicate that N-myc is require d for hepatocyte survival and suggest that it is involved in the genet ic cascade leading to normal liver development. (C) 1998 Academic Pres s.