A C-terminally truncated form of β-catenin acts as a novel regulator of Wnt/β-catenin signaling in planarians

beta-Catenin, the core element of the Wnt/beta-catenin pathway, is a multifunctional and evolutionarily conserved protein which performs essential roles in a variety of developmental and homeostatic processes. Despite its crucial roles, the mechanisms that control its contextspecific functions in time and space remain largely unknown. The Wnt/beta-catenin pathway has been extensively studied in planarians, flatworms with the ability to regenerate and remodel the whole body, providing a 'whole animal' developmental framework to approach this question. Here we identify a C-terminally truncated beta-catenin (beta-catenin4), generated by gene duplication, that is required for planarian photoreceptor cell specification. Our results indicate that the role of beta-catenin4 is to modulate the activity of beta-catenin1, the planarian beta-catenin involved in Wnt signal transduction in the nucleus, mediated by the transcription factor TCF-2. This inhibitory form of beta-catenin, expressed in specific cell types, would provide a novel mechanism to modulate nuclear beta-catenin signaling levels. Genomic searches and in vitro analysis suggest that the existence of a C-terminally truncated form of beta-catenin could be an evolutionarily conserved mechanism to achieve a fine-tuned regulation of Wnt/beta-catenin signaling in specific cellular contexts.