IPF1, A HOMEODOMAIN PROTEIN WITH A DUAL FUNCTION IN PANCREAS DEVELOPMENT

Insulin promoter factor 1 (IPF1), is a homeodomain protein which, in t he adult mouse pancreas, is selectively expressed in 13-cells, and whi ch binds to, and transactivates, the insulin promoter via the beta 1 e lement. In mouse embryos, IPF1 expression is initiated when the foregu t endoderm commits to a pancreatic fate, i.e. prior to both morphogene sis and hormone specific gene expression. At later stages of developme nt the expression is restricted to the dorsal and ventral walls of the primitive foregut at the positions where the pancreases will form. Mi ce homozygous for a targeted mutation in the Ipf1 gene selectively lac k the pancreas. The mutant pups develop to term and are born alive, bu t die after a few days. The gastrointestinal tract with its associated organs shows no obvious malformations. No pancreatic tissue and no ec topic expression of insulin or pancreatic amylase could be detected in this region in mutant neonates or embryos. These findings demonstrate that IPF1 is needed for the formation of the pancreas,:and suggest th at IPF1 acts to determine the fate of common pancreatic precursor cell s and/or to regulate their propagation. The lack of a pancreas in the Ipf1-deficient mutants, the pattern of IPF1 expression and its ability to stimulate insulin gene transcription, strongly suggest that IPF1 f unctions both in the early specification of the primitive gut to a pan creatic fate and in the maturation of the pancreatic beta-cell.