A novel genetic model to study mechanosignaling and its impact on YAP/TAZ activity in mammalian tissues

Regulation of F-actin dynamics is key for multiple aspects of cell biology. Recent work indicates that this is particularly significant for cells to correctly sense the mechanical properties of the microenvironment, and to respond by regulating the YAP/TAZ transcriptional coactivators, which ultimately control cell behavior in response to mechanical cues. Yet, whether the connection between F-actin dynamics and YAP/TAZ signaling is physiologically relevant in mammalian tissues, and dominant over the pleiotropic effects of F-actin, remains unaddressed. We will present data on a novel mouse knockout system enabling cell- autonomous regulation of F-actin dynamics, where we observe a potent upregulation of YAP/TAZ activity, leading to tissue hyperproliferation and organ overgrowth. This unveils an unprecedented signaling function for the F-actin cytoskeleton in the regulation of mammalian tissue homeostasis.