The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.

中文翻译：

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Cthrc1 是雪旺氏细胞髓鞘形成的负调节因子。

分析神经元和雪旺细胞之间初始相互作用的分子机制是理解髓鞘形成过程的关键问题。我们最近将 Cthrc1（含有 1 的胶原三螺旋重复序列）鉴定为与轴突相互作用后在施旺细胞中上调的基因。Cthrc1 编码一种分泌蛋白，以前显示其参与不同细胞类型的迁移和增殖。我们使用细胞培养中的 RNA 干扰敲低和过度表达该基因的转基因小鼠系，通过功能丧失和功能获得方法对雪旺细胞中的 Cthrc1 进行了功能分析。这项工作确定 Cthrc1 增强雪旺氏细胞增殖但阻止髓鞘形成。特别是，转基因动物髓鞘形成的时程分析表明，雪旺细胞中 Cthrc1 的过表达导致髓鞘形成延迟，细胞保持增殖状态。因此，我们的数据表明 Cthrc1 起着负调节作用，微调外周髓鞘形成的开始。