Genetic Evidence that Dorsal Spinal Oligodendrocyte Progenitor Cells are Capable of Myelinating Ventral Axons Effectively in Mice

Genetic Evidence that Dorsal Spinal Oligodendrocyte Progenitor Cells are Capable of Myelinating Ventral Axons Effectively in Mice
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遗传证据表明,小鼠背脊髓少突胶质细胞祖细胞能够有效地使腹侧轴突髓鞘化。

DOI:
10.1007/s12264-020-00593-5
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发表时间:
2020-10-13
影响因子:
5.6
通讯作者:
Xu, Xiaofeng
Xu, Xiaofeng
中科院分区:
医学2区
文献类型:
--
作者:
Fang, Minxi;Yu, Qian;Xu, Xiaofeng

文献摘要

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在发育中的脊髓中,大多数少突胶质细胞祖细胞(OPCs)在腹侧神经上皮中在Sonic Hedgehog(Shh)信号通路的控制下被诱导,而一小部分OPCs独立于Shh通路从背侧神经上皮细胞产生。虽然背侧衍生的OPC(dOPC)已被证明参与局部轴突髓鞘形成的背外侧区域在发展过程中,它是不知道他们是否能够迁移到腹侧区域和髓鞘腹侧轴突。在这项研究中,我们证实并扩展了以前的研究dOPCs的发展潜力,在缺乏腹源性OPCs(vOPCs)。在Nestin-Smo条件性基因敲除(cKO)小鼠中,当腹侧少突胶质细胞发生被阻断时,发现dOPCs经历快速扩增,扩散到腹侧脊髓组织,并最终在腹侧白色物质中分化成髓鞘化OL,具有时间延迟,提供了dOPCs能够在小鼠脊髓中使腹侧轴突髓鞘化的遗传证据。
In the developing spinal cord, the majority of oligodendrocyte progenitor cells (OPCs) are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog (Shh) signaling pathway, whereas a small subset of OPCs are generated from the dorsal neuroepithelial cells independent of the Shh pathway. Although dorsally-derived OPCs (dOPCs) have been shown to participate in local axonal myelination in the dorsolateral regions during development, it is not known whether they are capable of migrating into the ventral region and myelinating ventral axons. In this study, we confirmed and extended the previous study on the developmental potential of dOPCs in the absence of ventrally-derived OPCs (vOPCs). In Nestin-Smo conditional knockout (cKO) mice, when ventral oligodendrogenesis was blocked, dOPCs were found to undergo rapid amplification, spread to ventral spinal tissue, and eventually differentiated into myelinating OLs in the ventral white matter with a temporal delay, providing genetic evidence that dOPCs are capable of myelinating ventral axons in the mouse spinal cord.