Gone Caving: Roles of the Transcriptional Regulators YAP and TAZ in Skeletal Development.
PURPOSE OF REVIEW
The development of the skeleton is controlled by cellular decisions determined by the coordinated activation of multiple transcription factors. Recent evidence suggests that the transcriptional regulator proteins, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), could have important roles in directing the activity of these transcriptional programs. However, in vitro evidence for the roles of YAP and TAZ in skeletal cells has been hopelessly contradictory. The goals of this review are to provide a cross-sectional view on the state of the field and to synthesize the available data toward a unified perspective.


RECENT FINDINGS
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.
['Kegelman|Christopher D|CD|', 'Collins|Joseph M|JM|', 'Nijsure|Madhura P|MP|', 'Eastburn|Emily A|EA|', 'Boerckel|Joel D|JD|0000-0003-3126-3025']
D048868:Adaptor Proteins, Signal Transducing D001846:Bone Development D001857:Bone Matrix D017102:Fracture Healing D018507:Gene Expression Regulation, Developmental D006706:Homeostasis D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D014157:Transcription Factors D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins D000091102:YAP-Signaling Proteins
Transcription Development Bone Mechanotransduction Hippo pathway Osteogenesis