ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Mutation of 3-hydroxy-3-methylglutaryl CoA synthase I reveals requirements for isoprenoid and cholesterol synthesis in oligodendrocyte migration arrest, axon wrapping, and myelin gene expression.
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 55 papers.
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Who cites it
55 citing papers in PubMed, 98 citations in OpenAlex.
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- Mitochondria-Associated Endoplasmic Reticulum Membranes as Potential Therapeutic Targets in Epilepsy.CNS neuroscience & therapeutics · 2025Review
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- Oligodendrocyte arrangement, identification and morphology in the developing superior olivary complex.Frontiers in cellular neuroscience · 2025Article
- Electrical Synapses Mediate Embryonic Hyperactivity in a Zebrafish Model of Fragile X Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Regulators of Oligodendrocyte Differentiation.Cold Spring Harbor perspectives in biology · 2024Review
- Extracellular vesicle-associated cholesterol supports the regenerative functions of macrophages in the brain.Journal of extracellular vesicles · 2023Article
- High-fat diet plus HNF1A variant promotes polyps by activating β-catenin in early-onset colorectal cancer.JCI insight · 2023Article
- Raman spectroscopy and sciatic functional index (SFI) after low-level laser therapy (LLLT) in a rat sciatic nerve crush injury model.Lasers in medical science · 2022Article
- Human myelin proteolipid protein structure and lipid bilayer stacking.Cellular and molecular life sciences : CMLS · 2022Article
- Cholesterol biosynthesis defines oligodendrocyte precursor heterogeneity between brain and spinal cord.Cell reports · 2022Article
- Cholesterol in Brain Development and Perinatal Brain Injury: More than a Building Block.Current neuropharmacology · 2022Review
- Downregulation of low-density lipoprotein receptor mRNA in lymphatic endothelial cells impairs lymphatic function through changes in intracellular lipids.Theranostics · 2022Article
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- Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Myelin membrane, which ensheaths axons, has an unusually high amount of cholesterol. Cholesterol influences membrane fluidity and assembles lipid-rich microdomains within membranes, and some studies have shown that cholesterol is important for myelination. How cholesterol influences the development and differentiation of oligodendrocytes, glial cells that make myelin, is not known nor is clear whether isoprenoids, which also are products of the cholesterol biosynthetic pathway, contribute to myelination. Through a forward genetic screen in zebrafish we discovered that mutation of hmgcs1, which encodes an enzyme necessary for isoprenoid and cholesterol synthesis, causes oligodendrocyte progenitor cells (OPCs) to migrate past their target axons and to fail to express myelin genes. Drawing on a combination of pharmacological inhibitor and rescue experiments, we provide evidence that isoprenoids and protein prenylation, but not cholesterol, are required in OPCs to halt their migration at target axons. On the other hand, cholesterol, but not isoprenoids, is necessary both for axon ensheathment and myelin gene expression. Our data reveal that different products of the cholesterol biosynthetic pathway have distinct roles in oligodendrocyte development and that they together help to coordinate directed migration, axon wrapping, and gene expression.
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