Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury

  1. Matthew Grove
  2. Hyunkyoung Lee
  3. Huaqing Zhao
  4. Young-Jin Son  Is a corresponding author
  1. Temple University, United States

Abstract

Previously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.

Data availability

All data generated during this study are included in the manuscript.

Article and author information

Author details

  1. Matthew Grove

    Shriners Hospitals Pediatric Research Center, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hyunkyoung Lee

    Shriners Hospitals Pediatric Research Center, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Huaqing Zhao

    Department of Clinical Sciences, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Young-Jin Son

    Shriners Hospitals Pediatric Research Center, Temple University, Philadelphia, United States
    For correspondence
    yson@temple.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5725-9775

Funding

National Institute of Neurological Disorders and Stroke (NS105796)

  • Young-Jin Son

Shriners Hospitals for Children (Research award)

  • Young-Jin Son

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All surgical procedures and animal maintenance complied with the National Institute of Health guidelines regarding the care and use of experimental animals and were approved by the Institutional Animal Care and Use Committee of Temple University, Philadelphia, PA, USA. Protocol 4920

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: July 16, 2019
  2. Accepted: May 19, 2020
  3. Accepted Manuscript published: May 21, 2020 (version 1)
  4. Version of Record published: May 29, 2020 (version 2)

Copyright

© 2020, Grove et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Matthew Grove
  2. Hyunkyoung Lee
  3. Huaqing Zhao
  4. Young-Jin Son
(2020)
Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury
eLife 9:e50138.
https://doi.org/10.7554/eLife.50138
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