Lin28 Signaling Supports Mammalian PNS and CNS Axon Regeneration.

Lin28 Signaling Supports Mammalian PNS and CNS Axon Regeneration.
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Lin28 信号转导支持哺乳动物 PNS 和 CNS 轴突再生。

DOI:
10.1016/j.celrep.2018.07.105
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发表时间:
2018-09-04
期刊:
影响因子:
8.8
通讯作者:
Zhou FQ
Zhou FQ
中科院分区:
生物学1区
文献类型:
--
作者:
Wang XW;Li Q;Liu CM;Hall PA;Jiang JJ;Katchis CD;Kang S;Dong BC;Li S;Zhou FQ

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RNA结合蛋白Lin 28 a/B调节细胞生长和组织再生。在这里,我们研究了Lin 28在有丝分裂后神经元轴突再生控制中的作用。我们发现Lin 28 a/B通过其调控伙伴let-7 microRNAs(miRNAs)支持成熟感觉神经元轴突再生是必要的和充分的。更重要的是,Lin 28 a在成熟的视网膜神经节细胞(RGC)中的过表达产生稳健和持续的视神经再生。此外,RGC中Lin 28 a的组合过表达和Pten的下调可能通过减少再生RGC轴突的向后转动而相加地促进视神经再生。我们的研究结果不仅揭示了Lin 28信号在调节哺乳动物轴突再生中的重要作用,而且还确定了可以促进中枢神经系统(CNS)轴突再生的信号通路。在哺乳动物中枢神经系统轴突再生是一个挑战。Wang等人表明,Lin 28/let-7轴在外周神经系统中控制哺乳动物轴突再生中起重要作用。更重要的是,Lin 28 a的过表达诱导CNS中稳健和持续的轴突再生。
RNA-binding proteins Lin28a/b regulate cellular growth and tissue regeneration. Here, we investigated the role of Lin28 in the control of axon regeneration in postmitotic neurons. We find that Lin28a/b are both necessary and sufficient for supporting axon regeneration in mature sensory neurons through their regulatory partners, let-7 microRNAs (miRNAs). More importantly, overexpression of Lin28a in mature retinal ganglion cells (RGCs) produces robust and sustained optic nerve regeneration. Additionally, combined overexpression of Lin28a and downregulation of Pten in RGCs act additively to promote optic nerve regeneration, potentially by reducing the backward turning of regenerating RGC axons. Our findings not only reveal a vital role of Lin28 signaling in regulating mammalian axon regeneration but also identify a signaling pathway that can promote axon regeneration in the central nervous system (CNS). Axon regeneration in the mammalian CNS is a challenge. Wang et al. show that the Lin28/let-7 axis plays an important role in governing mammalian axon regeneration in the peripheral nervous system. More importantly, overexpression of Lin28a induces robust and sustained axon regeneration in the CNS.
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