Reelin/Disabled-1信号对斑马鱼脊髓损伤后功能恢复的影响

IF 1.6 4区 医学 Q3 DEVELOPMENTAL BIOLOGY
Rong Li, Sudhanshu Sahu
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引用次数: 0

摘要

Reelin是一种细胞外基质糖蛋白,在神经发育中起重要作用。在哺乳动物中,突变导致的其功能丧失会导致与运动协调受损、震颤和共济失调相关的严重疾病。关于Reelin在中枢神经系统损伤后功能恢复中的作用知之甚少。我们检测了Reelin及其下游信号转导分子Disabled-1 (Dab-1)的敲除对斑马鱼幼体脊髓损伤后功能恢复的影响。在每个分子上应用两个不重叠的反义morpholinos产生缺乏Reelin和Dab-1的幼虫。单独敲低Reelin和Dab-1的表达会损害损伤后的运动恢复,抑制再生轴突的髓鞘再生,减少损伤部位尾侧的运动神经元数量。这些结果表明,Reelin/Dab-1信号通路参与中枢神经系统损伤后轴突再生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Reelin/Disabled-1 Signalling Contributes to Functional Recovery on Zebrafish After Spinal Cord Injury

Reelin/Disabled-1 Signalling Contributes to Functional Recovery on Zebrafish After Spinal Cord Injury

Reelin, an extracellular matrix glycoprotein, plays important roles in neural development. Mutation-induced loss of its functions in mammals leads to severe disorders associated with impaired motor coordination, tremors and ataxia. Little is known about Reelin's role in functional recovery after central nervous system injury. We determined the effect of knock-down of Reelin and its downstream signal-transducing molecule Disabled-1 (Dab-1) on functional recovery after spinal cord injury in larval zebrafish. Larvae deficient in Reelin and Dab-1 were generated by application of two non-overlapping antisense morpholinos for each molecule. Individual knock-down of Reelin and Dab-1 expression impaired locomotor recovery after injury, inhibited remyelination of regrown axons and reduced numbers of motor neurons caudal to the lesion site. These results indicate that the Reelin/Dab-1 signalling pathway is involved in axon regeneration after injury of a paradigmatic vertebrate in the central nervous system.

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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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