1. Neuroscience
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YAP/TAZ initiate and maintain Schwann cell myelination

Research Article
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Cite this article as: eLife 2017;6:e20982 doi: 10.7554/eLife.20982

Abstract

Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis. Here we show that nuclear YAP/TAZ are essential regulators of peripheral nerve development and maintenance. To proliferate, developing Schwann cells (SCs) require YAP/TAZ to enter S-phase and, without them, fail to generate sufficient SCs for timely axon sorting. To differentiate, SCs require YAP/TAZ to upregulate Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy. Remarkably, in adulthood, nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in severe peripheral demyelination and mouse death. YAP/TAZ regulate both developmental and adult myelination by driving TEAD1 to activate Krox20. Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated nerve in adulthood. Our study also provides a new insight into the role of nuclear YAP/TAZ in homeostatic maintenance of an adult tissue.

Article and author information

Author details

  1. Matthew Grove

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hyukmin Kim

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maryline Santerre

    FELS Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander J Krupka

    Department of Bioengineering, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Seung Baek Han

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jinbin Zhai

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jennifer Y Cho

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Raehee Park

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Michele Harris

    Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Seonhee Kim

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Bassel E Sawaya

    FELS Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Shin H Kang

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Mary F Barbe

    Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Seo-Hee Cho

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Michel A Lemay

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

    Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, 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 (NS079631)

  • Young-Jin Son

Shriners Hospitals for Children (research grant,86600)

  • Young-Jin Son

National Institute of Neurological Disorders and Stroke (NS076401)

  • Bassel E Sawaya

National Institute of Mental Health (MH093331)

  • Bassel E Sawaya

National Institute of Neurological Disorders and Stroke (NS095070)

  • 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: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#4254, #4255) of the Temple University.

Reviewing Editor

  1. Klaus-Armin Nave, Max Planck Institute for Experimental Medicine,, Germany

Publication history

  1. Received: August 26, 2016
  2. Accepted: January 22, 2017
  3. Accepted Manuscript published: January 26, 2017 (version 1)
  4. Version of Record published: February 1, 2017 (version 2)

Copyright

© 2017, 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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