Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA.
Neural Dev. 2017 Aug 17;12(1):15. doi: 10.1186/s13064-017-0092-3.
After axon severing, neurons recover function by reinitiating axon outgrowth. New outgrowth often originates from the remaining axon stump. However, in many mammalian neurons, new axons initiate from a dendritic site when the axon is injured close to the cell body.
Drosophila sensory neurons are ideal for studying neuronal injury responses because they can be injured reproducibly in a variety of genetic backgrounds. In Drosophila, it has been shown that a complex sensory neuron, ddaC, can regenerate an axon from a stump, and a simple sensory neuron, ddaE, can regenerate an axon from a dendrite. To provide a more complete picture of axon regeneration in these cell types, we performed additional injury types.
We found that ddaE neurons can initiate regeneration from an axon stump when a stump remains. We also showed that ddaC neurons regenerate from the dendrite when the axon is severed close to the cell body. We next demonstrated if a stump remains, new axons can originate from this site and a dendrite at the same time. Because cutting the axon close to the cell body results in growth of the new axon from a dendrite, and cutting further out may not, we asked whether the initial response in the cell body was similar after both types of injury. A transcriptional reporter for axon injury signaling, puc-GFP, increased with similar timing and levels after proximal and distal axotomy. However, changes in dendritic microtubule polarity differed in response to the two types of injury, and were influenced by the presence of a scar at the distal axotomy site.
We conclude that both ddaE and ddaC can regenerate axons either from the stump or a dendrite, and that there is some feedback between the two sites that modulates dendritic microtubule polarity.
在轴突切断后，神经元通过重新启动轴突生长来恢复功能。新的生长通常起源于剩余的轴突残端。然而，在许多哺乳动物神经元中，当轴突在靠近细胞体的位置受伤时，新的轴突会从树突部位起始。
果蝇感觉神经元是研究神经元损伤反应的理想模型，因为它们可以在多种遗传背景下重复地被损伤。在果蝇中，已经表明一个复杂的感觉神经元 ddaC 可以从残端再生轴突，而一个简单的感觉神经元 ddaE 可以从树突再生轴突。为了更全面地了解这两种细胞类型中的轴突再生，我们进行了额外的损伤类型实验。
我们发现，当残端存在时，ddaE 神经元可以从轴突残端起始再生。我们还表明，当轴突在靠近细胞体的位置被切断时，ddaC 神经元会从树突再生。接下来，我们证明了当残端存在时，新的轴突可以同时从这个部位和树突起始生长。因为靠近细胞体切断轴突会导致新轴突从树突生长，而进一步切断则不会，所以我们想知道这两种损伤类型后，细胞体中的初始反应是否相似。轴突损伤信号的转录报告基因 puc-GFP 在近端和远端轴突切断后，以相似的时间和水平增加。然而，对两种损伤类型的反应，树突微管极性的变化不同，并且受到远端轴突切断部位疤痕的影响。
我们的结论是，ddaE 和 ddaC 都可以从残端或树突再生轴突，并且两个部位之间存在一些反馈，调节树突微管极性。
