Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium
Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium
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DOI：
10.1093/emboj/cdf649
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发表时间：
2002-12-02
期刊：
影响因子：
11.4
通讯作者：
Gradwohl, G
中科院分区：
文献类型：
--
作者：
Jenny, M;Uhl, C;Gradwohl, G
胰腺和胃肠道的内分泌细胞来源于多能内胚层干细胞。我们先前已经表明，碱性螺旋 - 环 - 螺旋（bHLH）转录因子神经元素3（ngn3）是发育中的胰腺未分化祖细胞内分泌谱系特化所必需的。在此我们研究了ngn3在肠道和胃上皮内分泌细胞发育控制中的表达及功能。我们的结果表明，如同在胰腺中一样，胃肠道内分泌细胞来源于表达ngn3的祖细胞。ngn3基因纯合缺失突变的小鼠无法产生任何肠道内分泌细胞，并且缺乏内分泌祖细胞。其他主要的肠道上皮细胞类型能够正常分化。相反，在腺胃中，胃泌素（G细胞）和生长抑素（D细胞）分泌细胞的分化受损，而表达5 - 羟色胺（肠嗜铬细胞EC细胞）、组胺（肠嗜铬样细胞ECL细胞）和胃饥饿素（X/A细胞）的细胞仍然存在。因此，ngn3是多能肠道祖细胞内分泌细胞命运特化所严格必需的，而胃内分泌细胞的发育既依赖ngn3又不依赖ngn3。
Endocrine cells of the pancreas and the gastrointestinal tract derive from multipotent endodermal stem cells. We have shown previously that the basic helix-loop-helix (bHLH) transcription factor neurogenin3 (ngn3) is required for the specification of the endocrine lineage in uncommitted progenitors in the developing pancreas. We investigate herein the expression and the function of ngn3 in the control of endocrine cell development in the intestinal and gastric epithelium. Our results indicate that as in the pancreas, gastrointestinal endocrine cells derive from ngn3-expressing progenitors. Mice homozygous for a null mutation in ngn3 fail to generate any intestinal endocrine cells, and endocrine progenitor cells are lacking. The other main intestinal epithelial cell types differentiate properly. In contrast, in the glandular stomach, the differentiation of the gastrin- (G cells) and somatostatin (D cells)-secreting cells is impaired whereas serotonin- (enterochromaffin EC cells), histamine(enterochromaffin-like ECL cells) and ghrelin (X/A cells)-expressing cells are still present. Thus, ngn3 is strictly required for endocrine cell fate specification in multipotent intestinal progenitor cells, whereas gastric endocrine development is both ngn3 dependent and independent.