Journal
GENES & DEVELOPMENT
Volume 16, Issue 12, Pages 1488-1497Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.985002
Keywords
basic-helix-loop-helix (bHLH) protein; neurogenin 3 (ngn3); notch signaling; metaplasia; enteroendocrine cells; iFABP; Muc 2
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Funding
- NIDDK NIH HHS [R01 DK53839, P30 DK019525, R01 DK55342, R01 DK053839, F32 DK61226-01, F32 DK061226, R01 DK055342, P30 DK050306] Funding Source: Medline
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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 stein cells to derive all 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.
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