Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination

  1. Liang Zhou
  2. Chong-Yu Shao
  3. Ya-Jun Xie
  4. Na Wang
  5. Si-Min Xu
  6. Ben-Yan Luo
  7. Zhi-Ying Wu
  8. Yue Hai Ke
  9. Mengsheng Qiu
  10. Ying Shen  Is a corresponding author
  1. Zhejiang University School of Medicine, China
  2. Zhejiang University City College, China
  3. Hangzhou Normal University, China

Abstract

Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is down-regulated by PDGF stimulation and up-regulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3β and regulated its activity, and thereby affects the nuclear accumulation of β-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Liang Zhou

    Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Chong-Yu Shao

    Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Ya-Jun Xie

    Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Na Wang

    School of Medicine, Zhejiang University City College, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Si-Min Xu

    Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Ben-Yan Luo

    Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Zhi-Ying Wu

    Department of Neurology and Research Center of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yue Hai Ke

    Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Mengsheng Qiu

    Institute of Life Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Ying Shen

    Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China
    For correspondence
    yshen@zju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7034-5328

Funding

Ministry of Science and Technology of the People's Republic of China (2017YFA0104200)

  • Ying Shen

National Natural Science Foundation of China (31571051)

  • Liang Zhou

National Natural Science Foundation of China (81625006)

  • Ying Shen

National Natural Science Foundation of China (31820103005)

  • Ying Shen

Natural Science Foundation of Zhejiang Province (Z15C090001)

  • Ying Shen

Natural Science Foundation of Zhejiang Province (LQ17C090001)

  • Na Wang

Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT31038)

  • Ying Shen

Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT31041)

  • Ying Shen

Chinese Ministry of Education Project 111 Program (B13026)

  • Ying Shen

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 of the animals were handled according to approved protocol (ZJU20160019) of the Animal Experimentation Ethics Committee of Zhejiang University.

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Publication history

  1. Received: September 20, 2019
  2. Accepted: January 14, 2020
  3. Accepted Manuscript published: January 16, 2020 (version 1)
  4. Version of Record published: January 27, 2020 (version 2)

Copyright

© 2020, Zhou 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. Liang Zhou
  2. Chong-Yu Shao
  3. Ya-Jun Xie
  4. Na Wang
  5. Si-Min Xu
  6. Ben-Yan Luo
  7. Zhi-Ying Wu
  8. Yue Hai Ke
  9. Mengsheng Qiu
  10. Ying Shen
(2020)
Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
eLife 9:e52056.
https://doi.org/10.7554/eLife.52056

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