A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination

Yaqi Deng, Lai Man Natalie Wu, Shujun Bai, Chuntao Zhao, Haibo Wang, Jincheng Wang, Lingli Xu, Masahide Sakabe, Wenhao Zhou, Mei Xin () and Q. Richard Lu ()
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Yaqi Deng: Cincinnati Children’s Hospital Medical Center
Lai Man Natalie Wu: Cincinnati Children’s Hospital Medical Center
Shujun Bai: 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
Chuntao Zhao: Cincinnati Children’s Hospital Medical Center
Haibo Wang: Cincinnati Children’s Hospital Medical Center
Jincheng Wang: Cincinnati Children’s Hospital Medical Center
Lingli Xu: Key Laboratory of Birth Defects, Children’s Hospital of Fudan University
Masahide Sakabe: Cincinnati Children’s Hospital Medical Center
Wenhao Zhou: Key Laboratory of Birth Defects, Children’s Hospital of Fudan University
Mei Xin: Cincinnati Children’s Hospital Medical Center
Q. Richard Lu: Cincinnati Children’s Hospital Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15161

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