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Dev Biol. 2012 May 1;365(1):175-88. doi: 10.1016/j.ydbio.2012.02.024. Epub 2012 Feb 24.

Arx is required for normal enteroendocrine cell development in mice and humans.

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  • 1Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, USA.

Abstract

Enteroendocrine cells of the gastrointestinal (GI) tract play a central role in metabolism, digestion, satiety and lipid absorption, yet their development remains poorly understood. Here we show that Arx, a homeodomain-containing transcription factor, is required for the normal development of mouse and human enteroendocrine cells. Arx expression is detected in a subset of Neurogenin3 (Ngn3)-positive endocrine progenitors and is also found in a subset of hormone-producing cells. In mice, removal of Arx from the developing endoderm results in a decrease of enteroendocrine cell types including gastrin-, glucagon/GLP-1-, CCK-, secretin-producing cell populations and an increase of somatostatin-expressing cells. This phenotype is also observed in mice with endocrine-progenitor-specific Arx ablation suggesting that Arx is required in the progenitor for enteroendocrine cell development. In addition, depletion of human ARX in developing human intestinal tissue results in a profound deficit in expression of the enteroendocrine cell markers CCK, secretin and glucagon while expression of a pan-intestinal epithelial marker, CDX2, and other non-endocrine markers remained unchanged. Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22387004
[PubMed - indexed for MEDLINE]
PMCID:
PMC3322318
Free PMC Article

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