Sancho Rocio, Cremona Catherine A, Behrens Axel
Mammalian Genetics Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK
Mammalian Genetics Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
EMBO Rep. 2015 May;16(5):571-81. doi: 10.15252/embr.201540188. Epub 2015 Apr 8.
The control of cell fate decisions is vital to build functional organs and maintain normal tissue homeostasis, and many pathways and processes cooperate to direct cells to an appropriate final identity. Because of its continuously renewing state and its carefully organised hierarchy, the mammalian intestine has become a powerful model to dissect these pathways in health and disease. One of the signalling pathways that is key to maintaining the balance between proliferation and differentiation in the intestinal epithelium is the Notch pathway, most famous for specifying distinct cell fates in adjacent cells via the evolutionarily conserved process of lateral inhibition. Here, we will review recent discoveries that advance our understanding of how cell fate in the mammalian intestine is decided by Notch and lateral inhibition, focusing on the molecular determinants that regulate protein turnover, transcriptional control and epigenetic regulation.
细胞命运决定的控制对于构建功能器官和维持正常组织稳态至关重要，许多信号通路和过程协同作用，引导细胞获得合适的最终身份。由于其持续更新的状态和精心组织的层级结构，哺乳动物肠道已成为剖析健康和疾病状态下这些信号通路的有力模型。Notch信号通路是维持肠道上皮细胞增殖和分化平衡的关键信号通路之一，它以通过进化上保守的侧向抑制过程在相邻细胞中指定不同细胞命运而闻名。在这里，我们将回顾最近的发现，这些发现加深了我们对Notch信号通路和侧向抑制如何决定哺乳动物肠道细胞命运的理解，重点关注调节蛋白质周转、转录控制和表观遗传调控的分子决定因素。
