Wnt signaling is sufficient to perturb oligodendrocyte maturation
Wnt signaling is sufficient to perturb oligodendrocyte maturation
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DOI：
10.1016/j.mcn.2009.07.010
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发表时间：
2009-10-01
影响因子：
3.5
通讯作者：
Grinspan, Judith B.
中科院分区：
文献类型：
--
作者：
Feigenson, Keith;Reid, Mary;Grinspan, Judith B.
少突胶质细胞是中枢神经系统的髓鞘形成细胞，其发育在时间和空间上受作为诱导剂或抑制剂的局部信号传导因子控制。背侧脊髓组织已被证明含有少突胶质细胞生成的抑制剂，尽管它们的身份还不完全清楚。我们已经研究了一个家庭的背部信号分子，Wnt，少突胶质细胞发育的行动。使用组织培养模型，我们已经表明，典型的Wnt活性通过β-连环蛋白激活抑制少突胶质细胞成熟，独立于前体细胞增殖，细胞死亡，或转移到一个替代的细胞命运。在少突胶质细胞谱系的细胞中组成性激活Wnt/β-连环蛋白信号传导的小鼠相对于对照同窝出生的小鼠具有相同数量的少突胶质细胞前体，但是在发育过程中延迟出现成熟的少突胶质细胞、髓鞘蛋白和有髓鞘轴突，尽管这些差异在成年时基本上消失。这些结果表明，激活Wnt/β-连环蛋白通路延迟了髓鞘形成少突胶质细胞的发育。(C)2009 Elsevier Inc. All rights reserved.
The development of oligodendrocytes, the myelinating cells of the central nervous system, is temporally and spatially controlled by local signaling factors acting as inducers or inhibitors. Dorsal spinal cord tissue has been shown to contain inhibitors of oligodendrogliogenesis, although their identity is not completely known. We have studied the actions of one family of dorsal signaling molecules, the Wnts, on oligodendrocyte development. Using tissue culture models, we have shown that canonical Wnt activity through beta-catenin activation inhibits oligodendrocyte maturation, independently of precursor proliferation, cell death, or diversion to an alternate cell fate. Mice in which Wnt/beta-catenin signaling was constitutively activated in cells of the oligodendrocyte lineage had equal numbers of oligodendrocyte precursors relative to control littermates, but delayed appearance of mature oligodendrocytes, myelin protein, and myelinated axons during development, although these differences largely disappeared by adulthood. These results indicate that activating the Wnt/beta-catenin pathway delays the development of myelinating oligodendrocytes. (C) 2009 Elsevier Inc. All rights reserved.