Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth
Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth
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DOI：
10.1073/pnas.1600564113
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发表时间：
2016-05-17
影响因子：
11.1
通讯作者：
Gabel, Christopher V.
中科院分区：
文献类型：
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作者：
Chung, Samuel H.;Awal, Mehraj R.;Gabel, Christopher V.
在发育过程中，神经元从快速生长状态转变为稳定形态，并且成年哺乳动物中枢神经系统内的神经元失去响应损伤而有效再生的能力。在这里，我们发现了一种新的神经元再生形式，它明显独立于 DLK-1/DLK、KGB-1/JNK 和其他已知介导秀丽隐杆线虫、果蝇和哺乳动物再生的 MAPK 信号因子。线虫中这种不依赖于 DLK 的再生与同一神经元类型中内源性活动依赖性异位轴突生长的经过充分研究的形式具有直接的遗传和分子联系。这两种神经元生长类型都是由感觉树突的物理损伤或破坏感觉活动的突变、钙信号传导或在神经元成熟过程中限制生长的基因（例如 SAX-1/NDR 激酶或 UNC-43/CaMKII）触发的。这些联系表明异位生长代表了神经元再生中基因发现的强大平台。此外，我们注意到线虫 DLK 独立再生和病变调理之间有许多相似之处，这是一种在哺乳动物中枢神经系统中产生强劲再生的现象。这两种再生类型都是由神经元活动减少导致感觉神经突损伤而触发，并通过破坏 L 型钙通道或升高 cAMP 来增强。总的来说，我们的研究将不同形式的神经元生长结合起来，以揭示对成人神经系统内在再生能力的活动依赖性控制的新分子见解。
During development, a neuron transitions from a state of rapid growth to a stable morphology, and neurons within the adult mammalian CNS lose their ability to effectively regenerate in response to injury. Here, we identify a novel form of neuronal regeneration, which is remarkably independent of DLK-1/DLK, KGB-1/JNK, and other MAPK signaling factors known to mediate regeneration in Caenorhabditis elegans, Drosophila, and mammals. This DLK-independent regeneration in C. elegans has direct genetic and molecular links to a well-studied form of endogenous activity-dependent ectopic axon outgrowth in the same neuron type. Both neuron outgrowth types are triggered by physical lesion of the sensory dendrite or mutations disrupting sensory activity, calcium signaling, or genes that restrict outgrowth during neuronal maturation, such as SAX-1/NDR kinase or UNC-43/CaMKII. These connections suggest that ectopic outgrowth represents a powerful platform for gene discovery in neuronal regeneration. Moreover, we note numerous similarities between C. elegans DLK-independent regeneration and lesion conditioning, a phenomenon producing robust regeneration in the mammalian CNS. Both regeneration types are triggered by lesion of a sensory neurite via reduction of neuronal activity and enhanced by disrupting L-type calcium channels or elevating cAMP. Taken as a whole, our study unites disparate forms of neuronal outgrowth to uncover fresh molecular insights into activity-dependent control of the adult nervous system's intrinsic regenerative capacity.