Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate
Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate
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DOI：
10.1016/j.ydbio.2007.07.015
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发表时间：
2007-09-15
影响因子：
2.7
通讯作者：
Samuelson, Linda C.
中科院分区：
文献类型：
--
作者：
Lopez-Diaz, Lymari;Jain, Renu N.;Samuelson, Linda C.
Neurogenin 3 对于肠内分泌细胞发育至关重要；然而，尚不清楚这种转录因子是否足以诱导肠道内的内分泌程序或它如何影响源自共同祖细胞的其他上皮细胞的发育。在这项研究中，小鼠绒毛启动子被用来驱动神经原蛋白 3 在整个发育上皮细胞中的表达，以测量对细胞命运的影响。尽管肠道的总体形态没有改变，但转基因创始胚胎表现出表达泛内分泌标记嗜铬粒蛋白 A 的细胞数量增加。因此，转基因中几种激素和促内分泌转录因子的表达增加，表明 Neurogenin 3 刺激了终末肠内分泌细胞发育程序。为了测试内分泌细胞分化的增加是否影响其他分泌细胞谱系的发育，我们量化了杯状细胞，这是胚胎肠中形成的唯一其他分泌细胞。表达神经原素 3 的转基因细胞的杯状细胞数量减少，与内分泌细胞的增加相对应，但分泌细胞总数没有变化。因此，我们的数据表明，Neurogenin 3 可以将双能分泌祖细胞的分化重新定向为内分泌细胞而非杯状细胞的命运。 (C) 2007 Elsevier Inc. 保留所有权利。
Neurogenin 3 is essential for enteroendocrine cell development; however, it is unknown whether this transcription factor is sufficient to induce an endocrine program in the intestine or how it affects the development of other epithelial cells originating from common progenitors. In this study, the mouse villin promoter was used to drive Neurogenin 3 expression throughout the developing epithelium to measure the affect on cell fate. Although the general morphology of the intestine was unchanged, transgenic founder embryos displayed increased numbers of cells expressing the pan-endocrine marker chromogranin A. Accordingly, expression of several hormones and pro-endocrine transcription factors was increased in the transgenics suggesting that Neurogenin 3 stimulated a program of terminal enteroendocrine cell development. To test whether increased endocrine cell differentiation affected the development of other secretory cell lineages, we quantified goblet cells, the only other secretory cell formed in embryonic intestine. The Neurogenin 3-expressing transgenics had decreased numbers of goblet cells in correspondence to the increase in endocrine cells, with no change in the total secretory cell numbers. Thus, our data suggest that Neurogenin 3 can redirect the differentiation of bipotential secretory progenitors to endocrine rather than goblet cell fate. (C) 2007 Elsevier Inc. All rights reserved.