Sox17 Promotes Oligodendrocyte Regeneration by Dual Modulation of Hedgehog and Wnt Signaling.
Sox17 Promotes Oligodendrocyte Regeneration by Dual Modulation of Hedgehog and Wnt Signaling.
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Sox17 通过 Hedgehog 和 Wnt 信号的双重调节促进少突胶质细胞再生。
DOI：
10.1016/j.isci.2020.101592
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发表时间：
2020-10-23
期刊：
影响因子：
5.8
通讯作者：
Chew LJ
中科院分区：
文献类型：
--
作者：
Ming X;Dupree JL;Gallo V;Chew LJ
促进少突胶质细胞发育的信号通路改善了少突胶质细胞的再生和脱髓鞘病变的髓鞘恢复。Sox因子严格控制髓鞘基因表达和少突胶质细胞的命运，但对Sox介导的少突胶质细胞再生的信号事件知之甚少。在SoxF成员Sox 17的这项研究中，我们证明了Sox 17诱导的少突胶质细胞再生在成年髓鞘病变中发生，通过抑制病变诱导的Wnt/β-连环蛋白信号，这是抑制少突胶质细胞再生和增加Sonic Hedgehog/Smoothened/Gli 2活性。通过Smoothened的Hedgehog信号传导非常支持成年少突胶质细胞的活力，并且是β-连环蛋白的上游调节因子。Gli 2在成年少突胶质细胞祖细胞中的消融表明Gli 2在野生型和Sox 17过表达的白色物质中调节β-连环蛋白的差异。尽管受到外源性Hedgehog刺激，但Sox 17缺陷小鼠的髓鞘病变仍表现出β-连环蛋白过度活化、再生失败和少突胶质细胞生成丧失。这些研究表明，Sox 17信号转导靶点通过调节Hedgehog和Wnt/β-连环蛋白信号转导来增强脱髓鞘损伤后的少突胶质细胞再生。Sox 17抑制脱髓鞘诱导的Wnt/β-catenin增加Sox 17增强Hedgehog信号在成人白色病变中的作用成人Hedgehog-Smoothened活性促进少突胶质细胞的维持Smoothened激活的少突胶质细胞再生依赖于Sox 17神经科学;分子神经科学;细胞生物学功能方面
Signaling pathways that promote oligodendrocyte development improve oligodendrocyte regeneration and myelin recovery from demyelinating pathologies. Sox factors critically control myelin gene expression and oligodendroglial fate, but little is known about signaling events underlying Sox-mediated oligodendroglial regeneration. In this study of the SoxF member Sox17, we demonstrate that Sox17-induced oligodendrocyte regeneration in adult myelin lesions occurs by suppressing lesion-induced Wnt/beta-catenin signaling which is inhibitory to oligodendrocyte regeneration and by increasing Sonic Hedgehog/Smoothened/Gli2 activity. Hedgehog signaling through Smoothened critically supports adult oligodendroglial viability and is an upstream regulator of beta-catenin. Gli2 ablation in adult oligodendrocyte progenitor cells indicates that Gli2 regulates beta-catenin differentially in wild-type and Sox17-overexpressing white matter. Myelin lesions in Sox17-deficient mice show beta-catenin hyperactivation, regenerative failure, and loss of oligodendrogenesis, despite exogenous Hedgehog stimulation. These studies indicate the benefit of Sox17 signaling targets to enhance oligodendrocyte regeneration after demyelination injury by modulating both Hedgehog and Wnt/beta-catenin signaling. Sox17 suppresses demyelination-induced Wnt/beta-catenin increase Sox17 enhances Hedgehog signaling in adult white matter lesions Adult Hedgehog-Smoothened activity promotes oligodendrocyte maintenance Oligodendrocyte regeneration by Smoothened activation is Sox17 dependent Neuroscience; Molecular Neuroscience; Functional Aspects of Cell Biology
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
7.3
作者：
Falkenstein, Kristin N.;Vokes, Steven A.
通讯作者：
Vokes, Steven A.
影响因子：
3.4
作者：
Li CT;Liu JX;Yu B;Liu R;Dong C;Li SJ
通讯作者：
Li SJ
影响因子：
6.2
作者：
Marcus, J;Honigbaum, S;Dupree, JL
通讯作者：
Dupree, JL
影响因子：
4.8
作者：
He, Jing;Sheng, Tao;Xie, Jingwu
通讯作者：
Xie, Jingwu