Mechanisms mediating intracellular sorting of Roundabout

我们运动、思考、学习、说话和控制身体都依赖于神经系统的正常运作。要做到这一点，我们所有的神经细胞都必须连接到大脑和它们控制的身体部位。大多数这种“连接在一起”发生在怀孕期间胚胎的生长发育过程中。要做到这一点，每个神经细胞必须延伸一个被称为轴突的漫长过程，跨越很长的距离，穿过复杂的环境，找到并连接到合适的合作伙伴。通过感知身体不同部位的特定化学物质或分子“线索”，每个轴突都会被引导何时转向以及以何种方式生长以到达其伴侣。这些信号由生长轴突顶端的“受体”蛋白质检测到。随着轴突生长到不同的区域，这些受体的活性会发生变化，我们希望找到在引导轴突沿其路径运行时控制这些受体活性的分子。我们已经知道，哺乳动物中的许多相同的分子和受体也存在于更小的动物中，比如果蝇，它们做同样的工作，但规模更小。我们正在用果蝇来描述其中一种名为RoundAbout的受体是如何在神经元的一个子集中受到调控的。我们知道，环形交叉路口必须受到精确的调控，轴突才能正确生长。虽然我们已经确定了回旋处蛋白的一个关键调节因子，但我们并不确切地知道这种分子是如何调节回旋处的。我们计划用果蝇作为一个模型系统，在那里我们可以准确地观察环形和无通讯分子在轴突生长过程中的行为。这将为我们提供有关这一过程动态的信息。我们还使用果蝇作为一个模型系统来快速识别和测试可能在这一过程中发挥作用的其他分子的作用，例如那些与CommIsless结合的分子。通过使用果蝇，我们可以减少在研究中牺牲大量小鼠的需要。一旦我们发现这些分子如何在果蝇身上发挥作用，我们就会通知其他研究人员，这样这些分子就可以在其他模型系统中进行测试。我们需要这些信息来了解神经系统是如何组成的，并找出哪些分子可能有助于我们修复导致瘫痪或神经退化的神经损伤或疾病。不幸的是，哺乳动物无法修复发生在大脑中的神经损伤，我们希望通过识别最初用于驱动和指导胚胎中神经细胞生长的分子，我们可以重新供应这些分子，以帮助人类神经细胞的再生。

We are dependent on our nervous system functioning correctly for us to move, think, learn, speak and control our bodies. To do this all our nerve cells must connect up in the brain and to the parts of the body they control. Most of this 'wiring together' happens during the growth and development of the embryo in pregnancy. To do this each nerve cell must extend a long process, called an axon, over large distances and through complex environments to find and connect to its appropriate partners. Each axon is guided when to turn and which way to grow to reach its partner by sensing specific chemicals or molecular 'cues' in different parts of the body. These signals are detected by 'receptor' proteins at the tip of the growing axon. The activity of these receptors change as the axons grow into different regions, We want to find the molecules that work to control the activity of these receptors as they guide axons along their pathways. We know already that many of the same molecules and receptors in mammals are also present in smaller animals like the fruitfly Drosophila where they do the same job but on a simpler scale. We are using Drosophila to characterise how one of these receptors called Roundabout is regulated in a subset of neurons. We know that Roundabout must be precisely regulated for axons to grow correctly. Although we have identied one key regulator of the Roundabout protein, a protein called Commissureless we do not know precisely how this molecule acts to regulate Roundabout. We plan to use Drosophila as a model system where we can watch exactly how the Roundabout and Commissureless molecules behave in the axons as they grow. This will give us information on the dynamics of the process. We also use Drosophila as a model system to rapidly identify and test the role of further molecules that may act in this process, e.g. those that bind to Commissureless. By using Drosophila we can reduce the need to sacrifice large numbers of mice in research. Once we have found out how these molecules work in Drosophila we will inform other researchers so that the molecules can be tested in other model systems. We need this information both to learn how the nervous system is made and to find out what molecules might be useful in helping us to repair neural injuries or diseases that lead to paralysis or neural degeneration. Unfortunately mammals cannot repair nerve damage that occurs in the brain, our hope is that by identifying the molecules that were originally used to drive and direct nerve cell growth in the embryo we can re-supply these molecules to help nerve cell regeneration in people.