| A gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathway |
| Li, DP; Dai, WX; Li, L; Zhou, ZH; Li, ZH; He, CZ; Li, XY; Lu, XY; Huang, QY; Zhu, YQ; Wu, DB; Lu, JQ; Yuan, YT; Zhao, YHC; Zhang, WB; Zeng, ZP; Wang, XM; Shi, P ; Zhang, L
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| 2026
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| 发表期刊 | Neuron
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| ISSN | 0896-6273
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| 卷号 | 114期号:10页码:1782-1799 |
| 摘要 | Evolutionary adaptations provide a powerful lens for discovering fundamental regulators. By studying a Retsat variant (Q247R) found in high-altitude-adapted species, we reveal a central pathway governing CNS myelination and repair. Mice harboring this variant show reduced neonatal hypoxia-induced hypomyelination and exhibit enhanced remyelination in adulthood. The variant exhibits heightened enzymatic activity, driving increased neuronal production of all-trans-13,14-dihydroretinol (ATDR). By ruling out an intrinsic role in oligodendrocytes, we define this pathway as non-cell autonomous. ATDR is converted in neurons to alltrans-dihydroretinoic acid, which acts as a neuron-to-glia paracrine signal to activate the RXR-gamma pathway in oligodendrocyte progenitor cells, thereby stimulating their differentiation and myelination. Administration of ATDR, a prodrug, potently promotes remyelination in multiple myelin injury models. Our work identifies Retsat and dihydroretinoids as pivotal regulators of white matter integrity and as a promising therapeutical avenue inspired by evolutionary genetics for white matter diseases. |
| 收录类别 | SCIE
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/14853
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| 专题 | 科研部门_进化与功能基因组学（施鹏）
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推荐引用方式
GB/T 7714 |
Li, DP,Dai, WX,Li, L,et al. A gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathway[J]. Neuron,2026,114(10):1782-1799.
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| APA |
Li, DP.,Dai, WX.,Li, L.,Zhou, ZH.,Li, ZH.,...&Zhang, L.(2026).A gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathway.Neuron,114(10),1782-1799.
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| MLA |
Li, DP,et al."A gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathway".Neuron 114.10(2026):1782-1799.
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