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The pancreatic and intestinal primordia contain epithelial progenitor cells that generate many cell types. During development, specific programs of gene expression restrict the developmental potential of such progenitors and promote their differentiation. The  Insm1  ( insulinoma-associated 1 ,  IA-1 ) gene encodes a Zinc-finger factor that was discovered in an insulinoma cDNA library. We show that pancreatic and intestinal endocrine cells express  Insm1  and require  Insm1  for their development. In the pancreas of  Insm1  mutant mice, endocrine precursors are formed, but only few insulin-positive β cells are generated. Instead, endocrine precursor cells accumulate that express none of the pancreatic hormones. A similar change is observed in the development of intestine, where endocrine precursor cells are formed but do not differentiate correctly. A hallmark of endocrine cell differentiation is the accumulation of proteins that participate in secretion and vesicle transport, and we find many of the corresponding genes to be down-regulated in  Insm1  mutant mice.  Insm1  thus controls a gene expression program that comprises hormones and proteins of the secretory machinery. Our genetic analysis has revealed a key role of  Insm1  in differentiation of pancreatic and intestinal endocrine cells.

The Zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic β cells and intestinal endocrine cells