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Microglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor

Author

Listed:
  • Amin Sherafat

    (University of Connecticut)

  • Friederike Pfeiffer

    (University of Connecticut
    University of Tübingen)

  • Alexander M. Reiss

    (University of Connecticut)

  • William M. Wood

    (University of Connecticut)

  • Akiko Nishiyama

    (University of Connecticut
    University of Connecticut
    University of Connecticut)

Abstract

Nerve-glia (NG2) glia or oligodendrocyte precursor cells (OPCs) are distributed throughout the gray and white matter and generate myelinating cells. OPCs in white matter proliferate more than those in gray matter in response to platelet-derived growth factor AA (PDGF AA), despite similar levels of its alpha receptor (PDGFRα) on their surface. Here we show that the type 1 integral membrane protein neuropilin-1 (Nrp1) is expressed not on OPCs but on amoeboid and activated microglia in white but not gray matter in an age- and activity-dependent manner. Microglia-specific deletion of Nrp1 compromised developmental OPC proliferation in white matter as well as OPC expansion and subsequent myelin repair after acute demyelination. Exogenous Nrp1 increased PDGF AA-induced OPC proliferation and PDGFRα phosphorylation on dissociated OPCs, most prominently in the presence of suboptimum concentrations of PDGF AA. These findings uncover a mechanism of regulating oligodendrocyte lineage cell density that involves trans-activation of PDGFRα on OPCs via Nrp1 expressed by adjacent microglia.

Suggested Citation

  • Amin Sherafat & Friederike Pfeiffer & Alexander M. Reiss & William M. Wood & Akiko Nishiyama, 2021. "Microglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22532-2
    DOI: 10.1038/s41467-021-22532-2
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    Cited by:

    1. Chang Hoon Cho & Ilana Vasilisa Deyneko & Dylann Cordova-Martinez & Juan Vazquez & Anne S. Maguire & Jenny R. Diaz & Abigail U. Carbonell & Jaafar O. Tindi & Min-Hui Cui & Roman Fleysher & Sophie Molh, 2023. "ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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