The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas

We have generated a mouse bearing a null allele of the gene encoding basic helix-loop-helix (bHLH) protein p48, the cell-specific DNA-binding subunit of hetero oligomeric transcription factor PTF1 that directs the expression of genes in the exocrine pancreas. The null mutation, which establishes a l ethal condition shortly after birth, leads to a complete absence of exocrin e pancreatic tissue and its specific products, indicating that p48 is requi red for differentiation and/or proliferation of the exocrine cell lineage. p48 is so far the only developmental regulator known to be required exclusi vely for committing cells to an exocrine fate. The hormone secreting cells of all four endocrine lineages are present in the mesentery that normally h arbors the pancreatic organ until day 16 of gestation. Toward the end of em bryonic life, cells expressing endocrine functions are no longer detected a t their original location but are now found to colonize the spleen, where t hey persist in a functional state until postnatal death of the organism occ urs. These findings suggest that the presence of the exocrine pancreas is r equired for the correct spatial assembly of the endocrine pancreas and that , in its absence, endocrine cells are directed by default to the spleen, a site that, in some reptiles, harbors part of this particular cellular compa rtment.