Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination

  1. Lin Pan
  2. Amelia Trimarco
  3. Alice J Zhang
  4. Ko Fujimori
  5. Yoshihiro Urade
  6. Lu O Sun
  7. Carla Taveggia  Is a corresponding author
  8. Ye Zhang  Is a corresponding author
  1. University of California, Los Angeles, United States
  2. IRCCS Ospedale San Raffaele, Italy
  3. Osaka Medical and Pharmaceutical University, Japan
  4. Daiichi University of Pharmacy, Japan
  5. The University of Texas Southwestern Medical Center, United States

Abstract

In the developing central nervous system, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes, which form myelin around axons. Oligodendrocytes and myelin are essential for the function of the central nervous system, as evidenced by the severe neurological symptoms that arise in demyelinating diseases such as multiple sclerosis and leukodystrophy. Although many cell-intrinsic mechanisms that regulate oligodendrocyte development and myelination have been reported, it remains unclear whether interactions among oligodendrocyte-lineage cells (OPCs and oligodendrocytes) affect oligodendrocyte development and myelination. Here, we show that blocking vesicle-associated membrane protein (VAMP) 1/2/3-dependent exocytosis from oligodendrocyte-lineage cells impairs oligodendrocyte development, myelination, and motor behavior in mice. Adding oligodendrocyte-lineage cell-secreted molecules to secretion-deficient OPC cultures partially restores the morphological maturation of oligodendrocytes. Moreover, we identified L-type prostaglandin D synthase as an oligodendrocyte-lineage cell-secreted protein that promotes oligodendrocyte development and myelination in vivo. These findings reveal a novel autocrine/paracrine loop model for the regulation of oligodendrocyte and myelin development.

Data availability

We deposited all RNA-seq data to the Gene Expression Omnibus under accession number GSE168569

The following data sets were generated

Article and author information

Author details

  1. Lin Pan

    Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  2. Amelia Trimarco

    Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy
    Competing interests
    No competing interests declared.
  3. Alice J Zhang

    Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  4. Ko Fujimori

    Department of Pathobiochemistry, Osaka Medical and Pharmaceutical University, Osaka, Japan
    Competing interests
    No competing interests declared.
  5. Yoshihiro Urade

    Daiichi University of Pharmacy, Fukuoka, Japan
    Competing interests
    No competing interests declared.
  6. Lu O Sun

    Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
  7. Carla Taveggia

    Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy
    For correspondence
    taveggia.carla@hsr.it
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6531-9544
  8. Ye Zhang

    Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    yezhang@ucla.edu
    Competing interests
    Ye Zhang, consulted for Ono Pharmaceutical..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1546-5930

Funding

UCLA Brain Research Institute (Knaub Postdoctoral Fellowship)

  • Lin Pan

Friends of the Semel Institute for Neuroscience & Human Behavior (Friends scholar award)

  • Ye Zhang

National Institute of Neurological Disorders and Stroke (R00NS089780)

  • Ye Zhang

National Institute of Neurological Disorders and Stroke (R01NS109025)

  • Ye Zhang

National Institute of Aging (R03AG065772)

  • Ye Zhang

National Institute of Child Health and Human Development (P50HD103557)

  • Ye Zhang

National Center for Advancing Translational Science UCLA CTSI Grant (UL1TR001881)

  • Ye Zhang

W. M. Keck Foundation (W. M. Keck Foundation junior faculty award)

  • Ye Zhang

UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (Innovation Award)

  • Ye Zhang

Wendy Ablon Foundation (Ablon Scholar Award)

  • Ye Zhang

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 animal experimental procedures (protocols: #R-16-079 and #R-16-080) were approved by the Chancellor's Animal Research Committee at the University of California, Los Angeles, and conducted in compliance with national and state laws and policies.

Reviewing Editor

  1. Kelly Monk, Vollum Institute, Oregon Health & Science University, United States

Publication history

  1. Received: January 29, 2022
  2. Preprint posted: February 14, 2022 (view preprint)
  3. Accepted: February 12, 2023
  4. Accepted Manuscript published: February 13, 2023 (version 1)
  5. Version of Record published: February 22, 2023 (version 2)

Copyright

© 2023, Pan 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. Lin Pan
  2. Amelia Trimarco
  3. Alice J Zhang
  4. Ko Fujimori
  5. Yoshihiro Urade
  6. Lu O Sun
  7. Carla Taveggia
  8. Ye Zhang
(2023)
Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination
eLife 12:e77441.
https://doi.org/10.7554/eLife.77441

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