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Status |
Public on Apr 26, 2017 |
Title |
A Reciprocal Regulatory Loop Between TAZ/YAP and G protein Gαs Regulates Schwann Cell Proliferation and Differentiation |
Organisms |
Mus musculus; Rattus norvegicus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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 direct role for Hippo effectors TAZ and YAP in regulation of 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 yet also required for their differentiation and myelination. Genome-wide occupancy mapping and transcriptome profiling reveal that nuclear TAZ and YAP promote SC proliferation by activating cell cycle regulators, while targeting critical differentiation regulators in cooperation with SOX10 for myelination. We further identified 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 myelination in the sciatic nerve. Thus, our study revealed that 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.
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Overall design |
3 Control Samples and 3 Mutant
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Contributor(s) |
Deng Y, Wu LM, Bai S, Lu Q |
Citation(s) |
28443644 |
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Submission date |
Feb 16, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Richard Lu |
Organization name |
Cincinnati Children's Hospital Medical Center
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Department |
CBDI
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Lab |
Lu Lab,T6.525
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Street address |
3333 Burnet Ave
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City |
Cincinnati |
State/province |
OH |
ZIP/Postal code |
45229 |
Country |
USA |
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Platforms (2) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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Samples (13)
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Relations |
BioProject |
PRJNA375093 |
SRA |
SRP100075 |