Sidestep-induced neuromuscular miswiring causes severe locomotion defects in Drosophila larvae
Sidestep-induced neuromuscular miswiring causes severe locomotion defects in Drosophila larvae
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DOI：
10.1242/dev.163279
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发表时间：
2018-09-01
期刊：
影响因子：
4.6
通讯作者：
Aberle, Hermann
中科院分区：
文献类型：
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作者：
Kinold, Jaqueline C.;Pfarr, Carsten;Aberle, Hermann
运动轴突导向分子的突变导致运动神经的异常投射模式。由于大多数对果蝇的研究都是在固定的胚胎中分析这些分子，因此对幼虫运动的影响是完全未知的。在这里，我们利用侧步（侧）突变幼虫，显示严重的运动缺陷，因为不可挽回的神经支配错误。侧的突变影响所有运动神经分支和所有体壁区域。神经支配缺陷是非刻板的，在每个半节段显示独特的神经支配模式。侧肌肉前体的过早激活废除运动神经的背侧迁移，导致幼虫的背侧肌肉上的神经肌肉接头完全丧失。高速摄像显示，这些幼虫未能保持基板接触，不适当地提出了头和尾节以上的基板，导致独特的“翘”和“升降”表型。这些结果表明，在侧突变体的指导错误，保持整个幼虫的生活，是不对称的双边身体轴。结合在小鼠身上的类似发现，这项研究还表明，错误的连接可能是遗传性运动障碍的潜在原因。
Mutations in motor axon guidance molecules cause aberrant projection patterns of motor nerves. As most studies in Drosophila have analysed these molecules in fixed embryos, the consequences for larval locomotion are entirely unexplored. Here, we took advantage of sidestep (side)-mutant larvae that display severe locomotion defects because of irreparable innervation errors. Mutations in side affected all motor nerve branches and all body wall regions. Innervation defects were non-stereotypical, showing unique innervation patterns in each hemisegment. Premature activation of Side in muscle precursors abrogated dorsal migration of motor nerves, resulting in larvae with a complete loss of neuromuscular junctions on dorsal-most muscles. High-speed videography showed that these larvae failed to maintain substrate contact and inappropriately raised both head and tail segments above the substrate, resulting in unique 'arching' and 'lifting' phenotypes. These results show that guidance errors in side mutants are maintained throughout larval life and are asymmetrical with respect to the bilateral body axis. Together with similar findings in mice, this study also suggests that miswiring could be an underlying cause of inherited movement disorders.