机构：[1]Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA.[2]Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu 610041, China.[3]Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.[4]Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai 201102, China.
Schwann cell (SC) myelination in the peripheral nervous system is essential for motor function, and uncontrolled SC proliferation occurs in cancer. Here, we show that a dual role for Hippo effectors TAZ and YAP in SC proliferation and myelination through modulating G-protein expression and interacting with SOX10, respectively. Developmentally regulated mutagenesis indicates that TAZ/YAP are critical for SC proliferation and differentiation in a stage-dependent manner. Genome-wide occupancy mapping and transcriptome profiling reveal that nuclear TAZ/YAP promote SC proliferation by activating cell cycle regulators, while targeting critical differentiation regulators in cooperation with SOX10 for myelination. We further identify that TAZ targets and represses Gnas, encoding Gαs-protein, which opposes TAZ/YAP activities to decelerate proliferation. Gnas deletion expands SC precursor pools and blocks peripheral myelination. Thus, the Hippo/TAZ/YAP and Gαs-protein feedback circuit functions as a fulcrum balancing SC proliferation and differentiation, providing insights into molecular programming of SC lineage progression and homeostasis.
基金：
US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01NS075243, R37NS096359]; National Multiple Sclerosis SocietyNational Multiple Sclerosis Society [NMSS-4727]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31400935]
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA.
共同第一作者：
通讯作者：
通讯机构：[1]Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA.[2]Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu 610041, China.[4]Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai 201102, China.
推荐引用方式(GB/T 7714)：
Yaqi Deng,Lai Man Natalie Wu,Shujun Bai,et al.A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination.[J].Nature communications.2017,8:15161.doi:10.1038/ncomms15161.
APA：
Yaqi Deng,Lai Man Natalie Wu,Shujun Bai,Chuntao Zhao,Haibo Wang...&Q. Richard Lu.(2017).A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination..Nature communications,8,
MLA：
Yaqi Deng,et al."A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination.".Nature communications 8.(2017):15161
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