The structure of Wntch signalling and the resolution of transition states in development

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 beta-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. (C) 2012 Elsevier Ltd. All rights reserved.