In mammals, the core Hippo signaling pathway is a kinase cascade composed of MST1/2, LATS1/2, SAV1, MOB1A/B, YAP/TAZ, the 14-3-3 protein that binds only to phosphorylated YAP/TAZ, and the TEAD transcription factors (TEAD1-4) that activates transcription of specific target genes upon binding to unphosphorylated YAP/TAZ. Finally, we will consider how increasing knowledge of YAP/TAZ signaling might influence the trajectory of future progress in regenerative medicine.įigure 2. Of particular interest is the key role of YAP/TAZ in maintaining the delicate balance between quiescence, self-renewal, proliferation and differentiation of endogenous adult stem cells within various tissues/organs during early development, normal homeostasis and regeneration/healing. In this review, we discuss the regulatory mechanisms by which YAP/TAZ control stem/progenitor cell differentiation into the various major lineages that are of interest to tissue engineering and regenerative medicine applications. The penultimate effectors of the Hippo signaling pathways YAP and TAZ, are transcriptional co-activator proteins that play key roles in many diverse biological processes, ranging from cell proliferation, tumorigenesis, mechanosensing and cell lineage fate determination, to wound healing and regeneration. 7Department of Biosystems Science and Engineering, ETH-Zürich, Basel, Switzerland.6Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.5IUTA Department Genie Biologique, Universite Claude Bernard Lyon 1, Villeurbanne, France.4National Engineering Laboratory for Digital and Material Technology of Stomatology, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, China.3Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, China.2Faculty of Science and Technology, Sunway University, Subang Jaya, Malaysia.1Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.Heng 1,2†, Xuehui Zhang 3,4†, Dominique Aubel 5, Yunyang Bai 6, Xiaochan Li 6, Yan Wei 6, Martin Fussenegger 7* and Xuliang Deng 4,6*
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