Neurogenin3 Initiates Stepwise Delamination of Differentiating Endocrine Cells During Pancreas Development
Neurogenin3 Initiates Stepwise Delamination of Differentiating Endocrine Cells During Pancreas Development
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DOI：
10.1002/dvdy.22544
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发表时间：
2011-03-01
影响因子：
2.5
通讯作者：
Grapin-Botton, Anne
中科院分区：
文献类型：
--
作者：
Gouzi, Mathieu;Kim, Yung Hae;Grapin-Botton, Anne
在发育过程中，胰腺内分泌细胞在胰腺上皮内特定。随后，它们从上皮中剥离，聚集在间质中，形成朗格汉斯胰岛。神经原蛋白3(Neurogenin3，Ngn3)是所有内分泌细胞分化所必需的转录因子，我们研究了它在细胞分层中的作用。我们在小鼠胰腺中观察到，大多数Ngn3阳性细胞已经与上皮腔失去了接触，这表明从祖细胞层剥离是由内分泌祖细胞启动的。随后，在小鼠和雏鸡中，新生的上皮边缘的内分泌细胞强烈减少E-钙粘附素，分解基板，并聚集成朗格汉斯胰岛。E-钙粘附素的抑制足以促进上皮细胞的分层。我们进一步证明，Ngn3在转录后间接调控Snail2蛋白的表达，从而抑制E-钙粘附素。在鸡胚中，Ngn3独立控制上皮细胞分层和分化程序。《发展动力学》240：589-604,2011。(C)2011年Wiley-Liss，Inc.
During development, pancreatic endocrine cells are specified within the pancreatic epithelium. They subsequently delaminate out of the epithelium and cluster in the mesenchyme to form the islets of Langerhans. Neurogenin3 (Ngn3) is a transcription factor required for the differentiation of all endocrine cells and we investigated its role in their delamination. We observed in the mouse pancreas that most Ngn3-positive cells have lost contact with the lumen of the epithelium, showing that the delamination from the progenitor layer is initiated in endocrine progenitors. Subsequently, in both mouse and chick newly born endocrine cells at the periphery of the epithelium strongly decrease E-cadherin, break-down the basal lamina and cluster into islets of Langerhans. Repression of E-cadherin is sufficient to promote delamination from the epithelium. We further demonstrate that Ngn3 indirectly controls Snail2 protein expression post-transcriptionally to repress E-cadherin. In the chick embryo, Ngn3 independently controls epithelium delamination and differentiation programs. Developmental Dynamics 240:589-604, 2011. (C) 2011 Wiley-Liss, Inc.