Functional Regeneration of the Sensory Root via Axonal Invasion
Functional Regeneration of the Sensory Root via Axonal Invasion
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DOI：
10.1016/j.celrep.2019.12.008
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发表时间：
2020-01-07
期刊：
影响因子：
8.8
通讯作者：
Smith, Cody J.
中科院分区：
文献类型：
--
作者：
Nichols, Ev L.;Smith, Cody J.
再生脊髓根撕脱后是广泛不成功的，尽管再生能力的其他PNS定位的神经。通过结合聚焦激光损伤模型根撕脱在斑马鱼，延时成像和转基因，我们确定再生DRG神经元不能重演的肌动蛋白为基础的入侵损伤后的发展模式。我们证明，通过药理学和遗传学方法在再生轴突中诱导肌动蛋白重组成侵入性成分可以拯救感觉轴突脊髓入口。使用组成性活性Src的细胞自主诱导入侵组分诱导DRG轴突再生，表明可以激活内在机制以驱动再生。此外，神经元活动和动物行为的分析显示，在刺激轴突通过侵入重新进入脊髓后，感觉回路活动和行为恢复。总而言之，我们的数据确定诱导侵入性成分足以在损伤后进行功能性感觉根再生。
Regeneration following spinal root avulsion is broadly unsuccessful despite the regenerative capacity of other PNS-located nerves. By combining focal laser lesioning to model root avulsion in zebrafish, time-lapse imaging, and transgenesis, we identify that regenerating DRG neurons fail to recapitulate developmental paradigms of actin-based invasion after injury. We demonstrate that inducing actin reorganization into invasive components via pharmacological and genetic approaches in the regenerating axon can rescue sensory axon spinal cord entry. Cell-autonomous induction of invasion components using constitutively active Src induces DRG axon regeneration, suggesting an intrinsic mechanism can be activated to drive regeneration. Furthermore, analyses of neuronal activity and animal behavior show restoration of sensory circuit activity and behavior upon stimulating axons to re-enter the spinal cord via invasion. Altogether, our data identify induction of invasive components as sufficient for functional sensory root regeneration after injury.