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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Cell Differentiation
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Cell Division
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Cell Lineage
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DNA-Binding Proteins / metabolism
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Digestive System / metabolism
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Enterochromaffin Cells / metabolism
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Enteroendocrine Cells / metabolism*
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Epithelial Cells / metabolism*
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Gastric Mucosa / metabolism
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Gastric Mucosa / pathology
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Gastrins / biosynthesis
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Gene Expression Regulation, Developmental
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Glucagon / biosynthesis
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Glucagon / metabolism
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Green Fluorescent Proteins
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Immunohistochemistry
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Luminescent Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Microscopy, Electron
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Microscopy, Fluorescence
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Models, Genetic
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / physiology*
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Oligonucleotide Array Sequence Analysis
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RNA / metabolism
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RNA, Messenger / metabolism
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Signal Transduction
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Somatostatin / biosynthesis
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Stomach / cytology*
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Transcription Factors / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Gastrins
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Luminescent Proteins
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Nerve Tissue Proteins
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Neurog3 protein, mouse
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RNA, Messenger
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Transcription Factors
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Green Fluorescent Proteins
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Somatostatin
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RNA
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Glucagon