From Stone to Sponge: Hippo/YAP Mechanotransduction Empowers Cell Fates and Functions in Bone and Liver

Cells experience and respond to both biochemical and mechanical signals throughout embryonic development and adult homeostasis. Bone and liver represent hard and soft tissues, respectively, and they are critically controlled by their mechanoenvironment. Although the significance of mechanotransduction, the process by which mechanical forces are converted into biological cues, has been acknowledged since the nineteenth century, only recent advances have begun to reveal the molecular underpinnings bridging biophysical stimuli and gene regulation. This review synthesizes the latest insights into mechanotransduction, with a focus on the Hippo/Yes-associated protein (YAP) pathway in development, regeneration, and disorders of the bone and liver, which are differentially controlled by mechanotransduction mediated by YAP/transcriptional coactivator with PDZ-binding motif (TAZ). Studies in bone and liver reveal that cells adapt to their distinct mechanoenvironment by differentially controlling their normal ranges of YAP/TAZ activities, deviation from which causes diseases.