Gone Caving: Roles of the Transcriptional Regulators YAP and TAZ in Skeletal Development.

YAP and TAZ are regulated by diverse upstream signals and interact downstream with multiple transcription factors involved in skeletal development, positioning YAP and TAZ as important signal integration nodes in an hourglass-shaped signaling pathway. Here, we provide a survey of putative transcriptional co-effectors for YAP and TAZ in skeletal cells. Synthesizing the in vitro data, we conclude that TAZ is consistently pro-osteogenic in function, while YAP can exhibit either pro- or anti-osteogenic activity depending on cell type and context. Synthesizing the in vivo data, we conclude that YAP and TAZ combinatorially promote developmental bone formation, bone matrix homeostasis, and endochondral fracture repair by regulating a variety of transcriptional programs depending on developmental stage. Here, we discuss the current understanding of the roles of the transcriptional regulators YAP and TAZ in skeletal development, and provide recommendations for continued study of molecular mechanisms, mechanotransduction, and therapeutic implications for skeletal disease.