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Vol. 16, No. 12, pp. 1488-1497, June 15, 2002
Department of Genetics, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104, USA
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.
[Key Words: Basic-helix-loop-helix (bHLH) protein; neurogenin 3 (ngn3); notch signaling; metaplasia; enteroendocrine cells; iFABP; Muc 2]
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