Oligodendrocyte Development in the Absence of Their Target Axons In Vivo.

Oligodendrocyte Development in the Absence of Their Target Axons In Vivo.
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DOI:
10.1371/journal.pone.0164432
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Lyons D
Lyons D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Almeida R;Lyons D

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少突胶质细胞在中枢神经系统的轴突周围形成髓磷脂,从而实现跳跃式传导。最近的研究表明,轴突可以调节少突胶质细胞发育和髓鞘形成的某些方面,然而,培养的少突胶质细胞在缺乏轴突和合成轴突样底物周围精心制作的髓鞘的情况下仍保留分化能力。目前尚不清楚少突胶质细胞的生命过程在多大程度上需要轴突的存在或来自轴突的信号。特别是,目前尚不清楚的是,在生物体中,决定髓鞘形成的特定轴突是否调节少突胶质细胞群,如果是的话,少突胶质细胞谱系进展的哪些精确步骤是由目标轴突调节的。在这里,我们使用斑马鱼幼虫的活体成像,这些幼虫携带标记少突胶质细胞谱系的转基因报告细胞,以研究当我们操纵目标轴突环境时,少突胶质细胞发育的哪些方面,从规范到分化受到影响。为了大幅减少髓鞘形成的轴突数量,我们使用了先前鉴定的激酶结合蛋白(kbp)突变体,其中脊髓中第一个有髓鞘的轴突,网状脊髓轴突,长度不能完全生长,在脊髓后部形成一个区域,其中大多数髓鞘形成的初始目标缺失。我们发现kbp突变体后脊髓网状脊髓轴突表面减少73%导致少突胶质细胞数量减少27%。通过对转基因OPC报告者的延时分析,我们发现少突胶质细胞数量的减少可以通过OPC增殖和存活的减少来解释。有趣的是,在几乎没有正常轴突目标的情况下,OPC规范和迁移没有改变。最后,我们发现OPCs向少突胶质细胞的及时分化完全不依赖于目标轴突的存在。总之,我们的数据说明了斑马鱼在改变的轴突环境中研究少突胶质细胞谱系的整个生命过程的能力。
Oligodendrocytes form myelin around axons of the central nervous system, enabling saltatory conduction. Recent work has established that axons can regulate certain aspects of oligodendrocyte development and myelination, yet remarkably oligodendrocytes in culture retain the ability to differentiate in the absence of axons and elaborate myelin sheaths around synthetic axon-like substrates. It remains unclear the extent to which the life-course of oligodendrocytes requires the presence of, or signals derived from axons in vivo. In particular, it is unclear whether the specific axons fated for myelination regulate the oligodendrocyte population in a living organism, and if so, which precise steps of oligodendrocyte-cell lineage progression are regulated by target axons. Here, we use live-imaging of zebrafish larvae carrying transgenic reporters that label oligodendrocyte-lineage cells to investigate which aspects of oligodendrocyte development, from specification to differentiation, are affected when we manipulate the target axonal environment. To drastically reduce the number of axons targeted for myelination, we use a previously identified kinesin-binding protein (kbp) mutant, in which the first myelinated axons in the spinal cord, reticulospinal axons, do not fully grow in length, creating a region in the posterior spinal cord where most initial targets for myelination are absent. We find that a 73% reduction of reticulospinal axon surface in the posterior spinal cord of kbp mutants results in a 27% reduction in the number of oligodendrocytes. By time-lapse analysis of transgenic OPC reporters, we find that the reduction in oligodendrocyte number is explained by a reduction in OPC proliferation and survival. Interestingly, OPC specification and migration are unaltered in the near absence of normal axonal targets. Finally, we find that timely differentiation of OPCs into oligodendrocytes does not depend at all on the presence of target axons. Together, our data illustrate the power of zebrafish for studying the entire life-course of the oligodendrocyte lineage in vivo in an altered axonal environment.
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发表时间: 2011-04-15
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DOI: 10.1038/nn.3992
发表时间: 2015-05
影响因子: 25
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发表时间: 1986-02
期刊: The Journal of cell biology
影响因子: --
作者:
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期刊: Current biology : CB
影响因子: --
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