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首页> 外文期刊>Biology Open >Experimental evidence for UNC-6 (netrin) axon guidance by stochastic fluctuations of intracellular UNC-40 (DCC) outgrowth activity
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Experimental evidence for UNC-6 (netrin) axon guidance by stochastic fluctuations of intracellular UNC-40 (DCC) outgrowth activity

机译：细胞内UNC-40（DCC）增生活动的随机波动指导UNC-6（netrin）轴突的实验证据

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How the direction of axon guidance is determined is not understood. In Caenorhabditis elegans the UNC-40 (DCC) receptor mediates a response to the UNC-6 (netrin) guidance cue that directs HSN axon development. UNC-40 becomes asymmetrically localized within the HSN neuron to the site of axon outgrowth. Here we provide experimental evidence that the direction of guidance can be explained by the stochastic fluctuations of UNC-40 asymmetric outgrowth activity. We find that the UNC-5 (UNC5) receptor and the cytoskeletal binding protein UNC-53 (NAV2) regulate the induction of UNC-40 localization by UNC-6. If UNC-40 localization is induced without UNC-6 by using an unc-53 mutation, the direction of UNC-40 localization undergoes random fluctuations. Random walk models describe the path made by a succession of randomly directed movement. This model was experimentally tested using mutations that affect Wnt/PCP signaling. These mutations inhibit UNC-40 localization in the anterior and posterior directions. As the axon forms in Wnt/PCP mutants, the direction of UNC-40 localization randomly fluctuates; it can localize in either the anterior, posterior, or ventral direction. Consistent with a biased random walk, over time the axon will develop ventrally in response to UNC-6, even though at a discrete time UNC-40 localization and outgrowth can be observed anterior or posterior. Also, axon formation is slower in the mutants than in wild-type animals. This is also consistent with a random walk since this model predicts that the mean square displacement (msd) will increase only linearly with time, whereas the msd increases quadratically with time for straight-line motion.
机译：轴突引导的方向如何确定尚不清楚。在秀丽隐杆线虫中，UNC-40（DCC）受体介导对指导HSN轴突发育的UNC-6（netrin）指导信号的反应。 UNC-40在HSN神经元内不对称地定位于轴突生长部位。在这里，我们提供实验证据，指导的方向可以通过UNC-40不对称增长活动的随机波动来解释。我们发现UNC-5（UNC5）受体和细胞骨架结合蛋白UNC-53（NAV2）调节UNC-6对UNC-40定位的诱导。如果通过使用unc-53突变在没有UNC-6的情况下诱导UNC-40定位，则UNC-40定位的方向会发生随机波动。随机游走模型描述了由一系列随机定向运动产生的路径。使用影响Wnt / PCP信号传导的突变，对该模型进行了实验测试。这些突变抑制UNC-40在前后方向上的定位。随着Wnt / PCP突变体中轴突的形成，UNC-40定位的方向随机波动。它可以定位在前，后或腹侧方向。与偏向随机行走相一致，即使在不连续的时间可以观察到UNC-40的定位和向外生长，轴突也会随着时间的推移而对UNC-6产生腹侧发育。而且，突变体中的轴突形成比野生型动物中的轴突形成慢。这也与随机游走是一致的，因为此模型预测均方位移（msd）仅随时间线性增加，而对于直线运动，msd随时间平方增加。

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