Lee Catherine S, Perreault Nathalie, Brestelli John E, Kaestner Klaus H
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Genes Dev. 2002 Jun 15;16(12):1488-97. doi: 10.1101/gad.985002.
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.
Notch信号通路对于包括胃肠道肠内分泌系统在内的多种组织中的内分泌细胞命运至关重要。肠内分泌细胞是腺胃胃上皮中发现的四种主要细胞类型之一。为了了解肠内分泌细胞发育的分子基础，我们利用小鼠胚胎干细胞中的基因靶向技术，获得了bHLH转录因子神经生成素3（ngn3）的一个EGFP标记的无效等位基因。在ngn3（-/-）小鼠中，腺胃上皮中缺乏分泌胰高血糖素的A细胞、分泌生长抑素的D细胞和分泌胃泌素的G细胞，而表达5-羟色胺的肠嗜铬（EC）细胞数量则显著减少。此外，ngn3（-/-）小鼠表现出胃上皮的肠化生。因此，ngn3是胃中肠内分泌细胞分化和胃上皮细胞特性维持所必需的。
