ArticleGlia2020
The mechanistic target of rapamycin pathway downregulates bone morphogenetic protein signaling to promote oligodendrocyte differentiation.
Article in Glia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- SOX10 Overexpression Enhances the Oligodendrocyte Lineage Commitment of iOPCs In Vitro by Reshaping Their Chromatin Binding Landscape.Bioengineering (Basel, Switzerland) · 2026Article
- Metabolic Reprogramming of Oligodendrocytes in Intrauterine Growth Restriction.Developmental neuroscience · 2026Article
- Spinal Cord Injury Remyelination: Pathways to Therapies.International journal of molecular sciences · 2025Review
- (Re)building the nervous system: A review of neuron-glia interactions from development to disease.Journal of neurochemistry · 2025Review
- Investigating the use of cuprizone and lysolecithin to model demyelinationFrontiers in cellular neuroscience · 2025Article
- Therapeutic potential and impact of nanoengineered patient-derived mesenchymal stem cells in a murine resection and recurrence model of human glioblastoma.Bioengineering & translational medicine · 2024Article
- The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury.BMC cardiovascular disorders · 2024Article
- Regulators of Oligodendrocyte Differentiation.Cold Spring Harbor perspectives in biology · 2024Review
- mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis.PloS one · 2024Article
- Signaling mechanisms involved in the regulation of remyelination in multiple sclerosis: a mini review.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Coordinated Regulation of Myelination by Growth Factor and Amino-acid Signaling Pathways.Neuroscience bulletin · 2023Review
- The AMPK activator metformin improves recovery from demyelination by shifting oligodendrocyte bioenergetics and accelerating OPC differentiation.Frontiers in cellular neuroscience · 2023Article
- Live-cell metabolic analysis of oligodendroglia isolated from postnatal mouse brain and spinal cord.STAR protocols · 2022Article
- Cholesterol biosynthesis defines oligodendrocyte precursor heterogeneity between brain and spinal cord.Cell reports · 2022Article
- p70S6 kinase regulates oligodendrocyte differentiation and is active in remyelinating lesions.Brain communications · 2022Article
- mTOR Signaling Regulates Metabolic Function in Oligodendrocyte Precursor Cells and Promotes Efficient Brain Remyelination in the Cuprizone Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Intrinsic and extrinsic regulators of oligodendrocyte progenitor proliferation and differentiation.Seminars in cell & developmental biology · 2021Article
- Review
- Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Oligodendrocyte precursor cells (OPCs) differentiate and mature into oligodendrocytes, which produce myelin in the central nervous system. Prior studies have shown that the mechanistic target of rapamycin (mTOR) is necessary for proper myelination of the mouse spinal cord and that bone morphogenetic protein (BMP) signaling inhibits oligodendrocyte differentiation, in part by promoting expression of inhibitor of DNA binding 2 (Id2). Here we provide evidence that mTOR functions specifically in the transition from early stage OPC to immature oligodendrocyte by downregulating BMP signaling during postnatal spinal cord development. When mTOR is deleted from the oligodendrocyte lineage, expression of the FK506 binding protein 1A (FKBP12), a suppressor of BMP receptor activity, is reduced, downstream Smad activity is increased and Id2 expression is elevated. Additionally, mTOR inhibition with rapamycin in differentiating OPCs alters the transcriptional complex present at the Id2 promoter. Deletion of mTOR in oligodendroglia in vivo resulted in fewer late stage OPCs and fewer newly formed oligodendrocytes in the spinal cord with no effect on OPC proliferation or cell cycle exit. Finally, we demonstrate that inhibiting BMP signaling rescues the rapamycin-induced deficit in myelin protein expression. We conclude that mTOR promotes early oligodendrocyte differentiation by suppressing BMP signaling in OPCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.