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PMID:16951258

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Citation

Gierl, MS, Karoulias, N, Wende, H, Strehle, M and Birchmeier, C (2006) The zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells. Genes Dev. 20:2465-78

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.

Links

PubMed PMC1560419 Online version:10.1101/gad.381806

Keywords

Animals; Cell Differentiation/genetics; Cell Differentiation/physiology; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Enteroendocrine Cells/cytology; Enteroendocrine Cells/secretion; Female; Gene Expression Regulation, Developmental; Humans; Insulin-Secreting Cells/cytology; Insulin-Secreting Cells/secretion; Intestinal Mucosa/cytology; Intestinal Mucosa/secretion; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Transcription Factors/biosynthesis; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/physiology; Zinc Fingers/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:INSM1

acts_upstream_of_or_within

GO:0003323: type B pancreatic cell development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3656035

P

Seeded From UniProt

complete

MOUSE:INSM1

acts_upstream_of_or_within

GO:0035270: endocrine system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3656035

P

Seeded From UniProt

complete


See also

References

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