A mathematical model explains saturating axon guidance responses to molecular gradients.
A mathematical model explains saturating axon guidance responses to molecular gradients.
复制标题
DOI：
10.7554/elife.12248
复制
发表时间：
2016-02-02
期刊：
影响因子：
7.7
通讯作者：
Goodhill GJ
中科院分区：
文献类型：
--
作者：
Nguyen H;Dayan P;Pujic Z;Cooper-White J;Goodhill GJ
正确的布线对神经系统的正常运作至关重要。分子梯度提供了关键的信号来引导生长锥，生长锥是发育中轴突的运动尖端，到达它们的目标。然而，在体外，生长锥跟踪高度随机的轨迹，以及分子梯度如何偏置它们的运动是不清楚的。在这里，我们介绍了一个数学模型的基础上持久性，偏见，和噪声来描述这种行为，直接由测量生长锥运动的详细统计数据在吸引力和排斥力的梯度在微流控装置的约束。该模型提供了一个数学解释，为什么平均轴突转向角在体外梯度饱和非常迅速地随着时间在相对较小的值。这项工作介绍了迄今为止最准确的生长锥轨迹预测模型，并加深了我们对体外和体内轴突引导事件的理解。DOI：http://dx.doi.org/10.7554/eLife.12248.001为了让你的大脑工作，数百万个神经细胞必须精确地连接在一起。为了实现这一点，生长中的神经纤维通过化学线索在发育中的大脑中导航。一个重要的线索是化学物质的浓度如何随着大脑的距离而变化。这种变化被称为化学梯度。然而，我们仍然不完全了解神经纤维如何利用这种梯度来控制自己。Nguyen等人建立了一个数学模型，解释了神经纤维对化学梯度的反应方式，并表明该模型与大鼠大脑神经纤维生长的新实验数据非常吻合。该模型表明，在某些条件下，神经纤维对化学梯度的反应令人惊讶地小。Nguyen等人“该模型现在可以用来预测神经纤维在许多其他情况下的反应，并可以帮助研究人员更多地了解大脑在发育过程中是如何连接起来的。该模型还可以揭示更多关于导致神经纤维响应化学梯度而急剧转向所需的条件。DOI：http://dx.doi.org/10.7554/eLife.12248.002网站
Correct wiring is crucial for the proper functioning of the nervous system. Molecular gradients provide critical signals to guide growth cones, which are the motile tips of developing axons, to their targets. However, in vitro, growth cones trace highly stochastic trajectories, and exactly how molecular gradients bias their movement is unclear. Here, we introduce a mathematical model based on persistence, bias, and noise to describe this behaviour, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model provides a mathematical explanation for why average axon turning angles in gradients in vitro saturate very rapidly with time at relatively small values. This work introduces the most accurate predictive model of growth cone trajectories to date, and deepens our understanding of axon guidance events both in vitro and in vivo. DOI: http://dx.doi.org/10.7554/eLife.12248.001 For your brain to work, millions of nerve cells have to be connected together precisely. To achieve this, growing nerve fibres navigate through the developing brain by following chemical cues. One important such cue is how the concentration of a chemical varies with distance across the brain. This variation is known as a chemical gradient. However we still don't fully understand exactly how nerve fibres use such gradients to steer themselves. Nguyen et al. have built a mathematical model that accounts for the way that nerve fibres respond to chemical gradients, and showed that the model closely matched new experimental data on the growth of nerve fibres from the rat brain. The model implies that, under some conditions, nerve fibres turn surprisingly little in response to a chemical gradient. Nguyen et al.’s model can now be used to predict nerve fibre responses in many other situations, and could help researchers to understand more about how the brain becomes wired up during development. The model could also reveal more about the conditions that are needed to cause nerve fibres to turn sharply in response to chemical gradients. DOI: http://dx.doi.org/10.7554/eLife.12248.002