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PMID: 12080087 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity.

Genes & development ·Vol. 16 ·No. 12 ·2002-06-15 ·Pages 1488-97

Lee CS, Perreault N, Brestelli JE, Kaestner KH

Abstract

The notch signaling pathway is essential for the endocrine cell fate in various tissues including the enteroendocrine system of the gastrointestinal tract. Enteroendocrine cells are one of the four major cell types found in the gastric epithelium of the glandular stomach. To understand the molecular basis of enteroendocrine cell development, we have used gene targeting in mouse embryonic stem cells to derive an EGFP-marked null allele of the bHLH transcription factor, neurogenin 3 (ngn3). In ngn3(-/-) mice, glucagon secreting A-cells, somatostatin secreting D-cells, and gastrin secreting G-cells are absent from the epithelium of the glandular stomach, whereas the number of serotonin-expressing enterochromaffin (EC) cells is decreased dramatically. In addition, ngn3(-/-) mice display intestinal metaplasia of the gastric epithelium. Thus, ngn3 is required for the differentiation of enteroendocrine cells in the stomach and the maintenance of gastric epithelial cell identity.

MeSH Terms
Alleles Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Division Cell Lineage DNA-Binding Proteins/metabolism Digestive System/metabolism Enterochromaffin Cells/metabolism Enteroendocrine Cells/metabolism Epithelial Cells/metabolism Gastric Mucosa/metabolism,pathology Gastrins/biosynthesis Gene Expression Regulation, Developmental Glucagon/biosynthesis,metabolism Green Fluorescent Proteins Immunohistochemistry Luminescent Proteins/metabolism Mice Mice, Inbred C57BL Microscopy, Electron Microscopy, Fluorescence Models, Genetic Nerve Tissue Proteins/genetics,physiology Oligonucleotide Array Sequence Analysis RNA/metabolism RNA, Messenger/metabolism Signal Transduction Somatostatin/biosynthesis Stomach/cytology Transcription Factors/metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors DNA-Binding Proteins Gastrins Luminescent Proteins Nerve Tissue Proteins Neurog3 protein, mouse RNA, Messenger Transcription Factors Green Fluorescent Proteins Somatostatin RNA Glucagon
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lee Catherine S
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Perreault Nathalie
Brestelli John E
Kaestner Klaus H
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.985002
Published
2002-06-15
Pages
1488-97
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC186338
Subset
IM
Grants
NIDDK NIH HHS · R01 DK53839 · United States
NIDDK NIH HHS · F32 DK061226 · United States
NIDDK NIH HHS · P30 DK050306 · United States
NIDDK NIH HHS · R01 DK055342 · United States
NIDDK NIH HHS · F32 DK61226-01 · United States
NIDDK NIH HHS · R01 DK053839 · United States
NIDDK NIH HHS · R01 DK55342 · United States
NIDDK NIH HHS · P30 DK019525 · United States
External Links
PubMed source DOI: 10.1101/gad.985002 PMC Full Text View journal details
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