Wu Zilu, Ghosh-Roy Anindya, Yanik Mehmet Fatih, Zhang Jin Z, Jin Yishi, Chisholm Andrew D
Division of Biological Sciences, Center for Molecular Genetics, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15132-7. doi: 10.1073/pnas.0707001104. Epub 2007 Sep 11.
We previously reported functional regeneration of Caenorhabditis elegans motor neurons after femtosecond laser axotomy. We report here that multiple neuronal types can regrow after laser axotomy using a variety of lasers. The precise pattern of regrowth varies with cell type, stage of animal, and position of axotomy. Mechanosensory axons cut in late larval or adult stages displayed extensive regrowth, yet failed to reach their target area because of guidance errors in the anteroposterior axis. By contrast, mechanosensory axons cut in early larval stages regrew at the same rate but with fewer anteroposterior guidance errors, and were more likely to reach their target area. In adult animals lacking the VAB-1 Eph receptor tyrosine kinase, mechanosensory axon regrowth was more accurate than in the wild type, suggesting that guidance errors of regrowing touch neuron axons are the result of Eph signaling. Kinase-dependent and kinase-independent Eph signaling influenced outgrowth and guidance of regrowing touch neurons, respectively. Mechanosensory neurons regrew when severed proximal to their collateral synaptic branch but did not regrow when severed distal to the branch point. However, the distal axon could regrow if the branch is removed surgically at the same time as distal axotomy, or at a later time. The touch neuron synaptic branch point may act as a sorting area to regulate growth. These findings reveal that multiple influences affect regenerative growth in C. elegans neurons.
我们之前报道了秀丽隐杆线虫运动神经元在飞秒激光轴突切断术后的功能性再生。我们在此报告，使用多种激光进行轴突切断术后，多种神经元类型均可再生。再生的精确模式因细胞类型、动物发育阶段以及轴突切断位置而异。在幼虫晚期或成虫阶段切断的机械感觉轴突显示出广泛的再生，但由于前后轴上存在导向错误，未能到达其目标区域。相比之下，在幼虫早期切断的机械感觉轴突以相同的速率再生，但前后导向错误较少，且更有可能到达其目标区域。在缺乏VAB - 1 Eph受体酪氨酸激酶的成年动物中，机械感觉轴突的再生比野生型更准确，这表明再生的触觉神经元轴突的导向错误是Eph信号传导的结果。激酶依赖性和激酶非依赖性Eph信号分别影响再生触觉神经元的生长和导向。当在其侧支突触分支近端切断时，机械感觉神经元会再生，但在分支点远端切断时则不会再生。然而，如果在远端轴突切断的同时或之后通过手术切除分支，则远端轴突可以再生。触觉神经元突触分支点可能作为一个分选区域来调节生长。这些发现揭示了多种因素影响秀丽隐杆线虫神经元的再生生长。
