Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination
- University of California, Los Angeles, United States
- IRCCS Ospedale San Raffaele, Italy
- Osaka Medical and Pharmaceutical University, Japan
- Daiichi University of Pharmacy, Japan
- 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
Article and author information
Author details
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.
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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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
