Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
Semin Cell Dev Biol. 2012 Jun;23(4):443-9. doi: 10.1016/j.semcdb.2012.01.012. Epub 2012 Feb 4.
During development, the emergence of different cell fates and their patterning into tissues and organs requires spatio-temporal coordination that controls the relative number of different cell types. Genetic analyses in different systems have revealed that interactions between Wnt and Notch signalling play pervasive roles in these processes. While many of these interactions can be explained in terms of transcriptional cross-talk between the effectors of these pathways, some of them require a different explanation. Experiments in Drosophila, Xenopus and mouse have revealed that Notch plays an important role in the modulation of the transcriptional activity of β-catenin (the main effector of Wnt signalling pathway, independently of its well characterized function as a membrane tethered transcription factor. These studies suggest that rather than two separate pathways, elements of Wnt and Notch signalling configure a single functional module, Wntch, that plays a key role in the resolution of cell fate decisions. Here we review the evidence for Wntch and present a current circuit view of the system, its control and its role in development with a special focus on stem cell populations.
在发育过程中,不同细胞命运的出现及其组织和器官的模式形成需要时空协调,以控制不同细胞类型的相对数量。不同系统中的遗传分析表明,Wnt 和 Notch 信号之间的相互作用在这些过程中发挥着普遍作用。虽然这些相互作用中的许多可以根据这些途径的效应物之间的转录交叉对话来解释,但其中一些需要不同的解释。果蝇、爪蟾和小鼠的实验表明,Notch 在调节β-catenin 的转录活性方面发挥着重要作用(Wnt 信号通路的主要效应物,而不考虑其作为膜连接转录因子的特征功能。这些研究表明,与其说是两个独立的途径,Wnt 和 Notch 信号的元素构成了一个单一的功能模块 Wntch,它在细胞命运决定的解决中起着关键作用。在这里,我们回顾了 Wntch 的证据,并提出了一个当前的系统电路观点,及其控制及其在发育中的作用,特别关注于干细胞群体。