The TSC1‐mTOR‐PLK axis regulates the homeostatic switch from Schwann cell proliferation to myelination in a stage‐specific manner

Minqing Jiang; Rohit Rao; Jincheng Wang; Jiajia Wang; Lingli Xu; Lai Man Wu; Jonah R. Chan; Huimin Wang; Q. Richard Lu

doi:10.1002/glia.23449

journal article May 03, 2018

The TSC1‐mTOR‐PLK axis regulates the homeostatic switch from Schwann cell proliferation to myelination in a stage‐specific manner

Minqing Jiang Rohit Rao Jincheng Wang

Jiajia Wang

Lingli Xu Lai Man Wu Jonah R. Chan

Huimin Wang

Q. Richard Lu

Glia Vol. 66 No. 9 pp. 1947-1959 · Wiley

View at Publisher Save 10.1002/glia.23449

Abstract

AbstractProper peripheral myelination depends upon the balance between Schwann cell proliferation and differentiation programs. The serine/threonine kinase mTOR integrates various environmental cues to serve as a central regulator of cell growth, metabolism, and function. We report here that tuberous sclerosis complex 1 (TSC1), a negative regulator of mTOR activity, establishes a stage‐dependent program for Schwann cell lineage progression and myelination by controlling cell proliferation and myelin homeostasis. Tsc1 ablation in Schwann cell progenitors in mice resulted in activation of mTOR signaling, and caused over‐proliferation of Schwann cells and blocked their differentiation, leading to hypomyelination. Transcriptome profiling analysis revealed that mTOR activation in Tsc1 mutants resulted in upregulation of a polo‐like kinase (PLK)‐dependent pathway and cell cycle regulators. Attenuation of mTOR or pharmacological inhibition of polo‐like kinases partially rescued hypomyelination caused by Tsc1 loss in the developing peripheral nerves. In contrast, deletion of Tsc1 in mature Schwann cells led to redundant and overgrown myelin sheaths in adult mice. Together, our findings indicate stage‐specific functions for the TSC1‐mTOR‐PLK signaling axis in controlling the transition from proliferation to differentiation and myelin homeostasis during Schwann cell development.

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Metrics

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Citations

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References

Details

Published: May 03, 2018
Vol/Issue: 66(9)
Pages: 1947-1959
License: View

Authors

M

Minqing Jiang

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio; The Institute of Cognitive Neuroscience, East China Normal University Shanghai China

R

Rohit Rao

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio

J

Jincheng Wang

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio

J

Jiajia Wang

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio; Key Laboratory of Birth Defects Children's Hospital of Fudan University Shanghai China

L

Lingli Xu

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio

L

Lai Man Wu

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio

J

Jonah R. Chan

Department of Neurology and Programs in Biomedical and Neurosciences University of California San Francisco California

H

Huimin Wang

The Institute of Cognitive Neuroscience, East China Normal University Shanghai China

Q

Q. Richard Lu

Department of Pediatrics, Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, University of Cincinnati Cincinnati Ohio; Key Laboratory of Birth Defects Children's Hospital of Fudan University Shanghai China

Funding

National Institutes of Health Award: R01NS072427

National Natural Science Foundation of China Award: 31271134

National Multiple Sclerosis Society Award: NMSS‐4727

Cite This Article

Minqing Jiang, Rohit Rao, Jincheng Wang, et al. (2018). The TSC1‐mTOR‐PLK axis regulates the homeostatic switch from Schwann cell proliferation to myelination in a stage‐specific manner. Glia, 66(9), 1947-1959. https://doi.org/10.1002/glia.23449

The TSC1‐mTOR‐PLK axis regulates the homeostatic switch from Schwann cell proliferation to myelination in a stage‐specific manner

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