Kokubu Hiroshi, Ohtsuka Toshiyuki, Kageyama Ryoichiro
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Genes Cells. 2008 Jan;13(1):41-51. doi: 10.1111/j.1365-2443.2007.01146.x.
In the epithelium of the developing glandular stomach, neuroendocrine cells differentiate from common progenitors, but the mechanism of how these cells are specified remains to be determined. Here, we show that the basic helix-loop-helix (bHLH) gene, mammalian achaete-scute homologue 1 (Mash1), is highly expressed in the glandular stomach epithelium. In Mash1-null mice, almost all gastric neuroendocrine cells are missing, whereas development of non-neuroendocrine cells is not significantly affected. The bHLH gene Neurogenin3 (Ngn3), which is known to regulate formation of subsets of gastric neuroendocrine cells (gastrin-, glucagon- and somatostatin-producing cells), is expressed normally in the Mash1-null stomach. Thus, Ngn3 alone is not sufficient but Mash1 is additionally required for the differentiation of these neuroendocrine cells. Taken together, these results indicate that formation of gastrin-, glucagon- and somatostatin-producing cells depends on both Mash1 and Ngn3, while that of other neuroendocrine cells depends on Mash1 alone, suggesting that combinations of bHLH genes may contribute to cell type diversity.
在发育中的腺胃上皮中，神经内分泌细胞由共同祖细胞分化而来，但这些细胞如何被特化的机制仍有待确定。在此，我们发现碱性螺旋-环-螺旋（bHLH）基因——哺乳动物无刚毛-缺刻同源物1（Mash1）——在腺胃上皮中高度表达。在Mash1基因敲除小鼠中，几乎所有胃神经内分泌细胞都缺失，而非神经内分泌细胞的发育未受到显著影响。已知调控胃神经内分泌细胞亚群（产生胃泌素、胰高血糖素和生长抑素的细胞）形成的bHLH基因神经生成素3（Ngn3），在Mash1基因敲除的胃中正常表达。因此，仅Ngn3不足以促使这些神经内分泌细胞分化，而Mash1是这些细胞分化所额外需要的。综上所述，这些结果表明，产生胃泌素、胰高血糖素和生长抑素的细胞的形成依赖于Mash1和Ngn3两者，而其他神经内分泌细胞的形成仅依赖于Mash1，这表明bHLH基因的组合可能促成了细胞类型的多样性。
