Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
Department of Biological Sciences, California State University East Bay, Hayward, CA 94542, USA.
Cell Rep. 2017 Sep 19;20(12):2955-2965. doi: 10.1016/j.celrep.2017.08.083.
The disproportionate length of an axon makes its structural and functional maintenance a major task for a neuron. The heterochronic gene lin-14 has previously been implicated in regulating the timing of key developmental events in the nematode C. elegans. Here, we report that LIN-14 is critical for maintaining neuronal integrity. Animals lacking lin-14 display axonal degeneration and guidance errors in both sensory and motor neurons. We demonstrate that LIN-14 functions both cell autonomously within the neuron and non-cell autonomously in the surrounding tissue, and we show that interaction between the axon and its surrounding tissue is essential for the preservation of axonal structure. Furthermore, we demonstrate that lin-14 expression is only required during a short period early in development in order to promote axonal maintenance throughout the animal's life. Our results identify a crucial role for LIN-14 in preventing axonal degeneration and in maintaining correct interaction between an axon and its surrounding tissue.
轴突的不成比例长度使得其结构和功能的维持成为神经元的主要任务。异时基因 lin-14 先前被认为参与调节线虫 C. elegans 中关键发育事件的时间。在这里,我们报告说 LIN-14 对于维持神经元的完整性是至关重要的。缺乏 lin-14 的动物在感觉和运动神经元中表现出轴突退化和导向错误。我们证明 LIN-14 既在神经元中自主发挥作用,也在周围组织中非自主发挥作用,并且我们表明轴突与其周围组织之间的相互作用对于维持轴突结构是必不可少的。此外,我们证明 lin-14 的表达仅在发育早期的短时间内是必需的,以促进整个动物生命周期中的轴突维持。我们的结果确定了 LIN-14 在防止轴突退化和维持轴突与其周围组织之间正确相互作用方面的关键作用。