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

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Official URL:https://doi.org/10.1101/gad.381806
PubMed:View item in PubMed
Creators Name:Gierl, M.S. and Karoulias, N. and Wende, H. and Strehle, M. and Birchmeier, C.
Journal Title:Genes & Development
Journal Abbreviation:Genes Dev
Volume:20
Number:17
Page Range:2465-2478
Date:1 September 2006
Keywords:Insm1, Development, Endocrine, Intestine, Pancreas, Animals, Mice
Abstract: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 beta 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.
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Item Type:Article

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