Microglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor.
Animals
Cell Differentiation
Cell Lineage
Cell Proliferation
Cells, Cultured
Cerebellum
/ cytology
Corpus Callosum
/ cytology
Demyelinating Diseases
/ chemically induced
Disease Models, Animal
Female
Humans
Lysophosphatidylcholines
/ administration & dosage
Male
Mice
Mice, Transgenic
Microglia
/ drug effects
Microscopy, Electron, Transmission
Models, Animal
Myelin Sheath
/ metabolism
Neuropilin-1
/ genetics
Oligodendrocyte Precursor Cells
/ physiology
Oligodendroglia
/ physiology
Platelet-Derived Growth Factor
/ metabolism
Primary Cell Culture
Receptor, Platelet-Derived Growth Factor alpha
/ metabolism
Remyelination
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
16
01
2020
accepted:
08
03
2021
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
4
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33859199
doi: 10.1038/s41467-021-22532-2
pii: 10.1038/s41467-021-22532-2
pmc: PMC8050320
doi:
Substances chimiques
Lysophosphatidylcholines
0
Platelet-Derived Growth Factor
0
platelet-derived growth factor A
0
Neuropilin-1
144713-63-3
Receptor, Platelet-Derived Growth Factor alpha
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2265Subventions
Organisme : NINDS NIH HHS
ID : R01 NS073425
Pays : United States
Organisme : NIH HHS
ID : S10 OD016435
Pays : United States
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