Notch signalling controls pancreatic cell differentiation
Notch signalling controls pancreatic cell differentiation
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DOI：
10.1038/23716
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发表时间：
1999-08-26
期刊：
影响因子：
64.8
通讯作者：
Edlund, H
中科院分区：
文献类型：
--
作者：
Apelqvist, Å;Li, H;Edlund, H
胰腺既有外分泌细胞，也有内分泌细胞，但控制这些细胞类型分化的分子机制在很大程度上是未知的。尽管胰腺内分泌细胞起源于内胚层，但它们与神经元(1-5)有几个共同的分子特征，并且，就像中枢神经系统(6，7)中的神经元一样，胰腺中分化的内分泌细胞以分散的方式出现在祖细胞线圈(8，9)的区域中。这表明它们可以通过Notch信令(6，7)按横向规范产生。在这里，为了验证这一观点，我们分析了在Notch信号通路的几个步骤中发生基因改变的小鼠的胰腺发育，缺乏Delta-like基因1(DL1)(10)或细胞内介质RBP-JK(11)的小鼠表现出胰腺内分泌细胞的加速分化。在过度表达神经原蛋白3(NGN 3)(12)或细胞内形式的Notch3(参考文献)的小鼠中也观察到类似的表型。13)(Notch信号的抑制因子)。这些数据提供了证据，证明NGN3作为前内分泌基因，并且Notch信号在发育中的胰腺的内分泌和前体/外分泌命运之间的决定是至关重要的。
The pancreas contains both exocrine and endocrine cells, but the molecular mechanisms controlling the differentiation of these cell types are largely unknown. Despite their endodermal origin, pancreatic endocrine cells share several molecular characteristics with neurons(1-5), and, like neurons in the central nervous system(6,7) differentiating endocrine cells in the pancreas appear in a scattered fashion within a field of progenitor coils(8,9). This indicates that they may be generated by lateral specification through Notch signalling(6,7). Here, to test this idea, we analysed pancreas development in mice genetically altered at several steps in the Notch signalling pathway, Mice deficient for Delta-like gene 1 (Dll1)(10) or the intracellular mediator RBP-JK(11) showed accelerated differentiation of pancreatic endocrine cells. A similar phenotype was observed in mice over-expressing neurogenin 3 (ngn 3)(12) or the intracellular form of Notch3 (ref. 13) (a repressor of Notch signalling). These data provide evidence that ngn3 acts as pro-endocrine gene and that Notch signalling is critical for the decision between the endocrine and progenitor/exocrine fates in the developing pancreas.