ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Oligodendrocyte precursor cell-intrinsic effect of Rheb1 controls differentiation and mediates mTORC1-dependent myelination in brain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 67 citations in OpenAlex.
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- High-rate mechano-stimulation alters proliferation- and maturation-related signaling of oligodendrocyte precursor cells in a 3D hydrogel.Mechanobiology in medicine · 2025Article
- SRSF10 regulates oligodendrocyte differentiation during mouse central nervous system development by modulating pre-mRNA splicing.Nucleic acids research · 2025Article
- Long-Term Excessive Alcohol Consumption Enhances Myelination in the Mouse Nucleus Accumbens.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Development of Oligodendroglia and Myelin.Advances in neurobiology · 2025Review
- mTOR signaling and Alzheimer's disease: What we know and where we are?CNS neuroscience & therapeutics · 2024Review
- Article
- Disruption of neuronal RHEB signaling impairs oligodendrocyte differentiation and myelination through mTORC1-DLK1 axis.Cell reports · 2023Article
- A zebrafish model of combined saposin deficiency identifies acid sphingomyelinase as a potential therapeutic target.Disease models & mechanisms · 2023Article
- Coordinated Regulation of Myelination by Growth Factor and Amino-acid Signaling Pathways.Neuroscience bulletin · 2023Review
- Myelin lipid metabolism and its role in myelination and myelin maintenance.Innovation (Cambridge (Mass.)) · 2023Review
- Recent Reports on Redox Stress-Induced Mitochondrial DNA Variations, Neuroglial Interactions, and NMDA Receptor System in Pathophysiology of Schizophrenia.Molecular neurobiology · 2022Review
- GATOR2 complex-mediated amino acid signaling regulates brain myelination.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors.Frontiers in pharmacology · 2022Review
- Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver.Frontiers in cell and developmental biology · 2022Article
- Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders.Frontiers in neurology · 2022Article
- The Akt-mTOR Pathway Drives Myelin Sheath Growth by Regulating Cap-Dependent Translation.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
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Rheb1 is an immediate early gene that functions to activate mammalian target of rapamycin (mTor) selectively in complex 1 (mTORC1). We have demonstrated previously that Rheb1 is essential for myelination in the CNS using a Nestin-Cre driver line that deletes Rheb1 in all neural cell lineages, and recent studies using oligodendrocyte-specific CNP-Cre have suggested a preferential role for mTORC1 is myelination in the spinal cord. Here, we examine the role of Rheb1/mTORC1 in mouse oligodendrocyte lineage using separate Cre drivers for oligodendrocyte progenitor cells (OPCs) including Olig1-Cre and Olig2-Cre as well as differentiated and mature oligodendrocytes including CNP-Cre and Tmem10-Cre. Deletion of Rheb1 in OPCs impairs their differentiation to mature oligodendrocytes. This is accompanied by reduced OPC cell-cycle exit suggesting a requirement for Rheb1 in OPC differentiation. The effect of Rheb1 on OPC differentiation is mediated by mTor since Olig1-Cre deletion of mTor phenocopies Olig1-Cre Rheb1 deletion. Deletion of Rheb1 in mature oligodendrocytes, in contrast, does not disrupt developmental myelination or myelin maintenance. Loss of Rheb1 in OPCs or neural progenitors does not affect astrocyte formation in gray and white matter, as indicated by the pan-astrocyte marker Aldh1L1. We conclude that OPC-intrinsic mTORC1 activity mediated by Rheb1 is critical for differentiation of OPCs to mature oligodendrocytes, but that mature oligodendrocytes do not require Rheb1 to make myelin or maintain it in the adult brain. These studies reveal mechanisms that may be relevant for both developmental myelination and impaired remyelination in myelin disease.
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Registered trials
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