Mechanisms mediating axon outgrowth in the Drosophila CNS

我们的行动、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必须在大脑和它们控制的身体部位连接在一起。大多数这种“连接在一起”发生在怀孕期间胚胎的生长和发育期间。要做到这一点，每个神经细胞必须延伸一个长长的过程，称为轴突，跨越很远的距离，穿过复杂的环境，找到并连接到合适的伙伴。通过感知身体不同部位的特定化学物质或分子“线索”，每个轴突都被引导何时转向，向哪个方向生长，以到达它的伴侣。这些信号被生长轴突尖端的“受体”蛋白检测到。这些受体的活动将信息传递到轴突以指导其生长。为了使这有效地发生，神经细胞必须协调其内部组织与外部信号。通过研究这些过程，我们将更好地理解神经系统是如何形成的，我们可以应用这些知识来帮助开发修复遭受神经损伤或疾病的患者神经系统的策略。我们想要找到控制轴突生长的分子来引导它沿着它的路径生长。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较小的动物中，比如果蝇，它们做同样的工作，但规模更简单。我们正在用果蝇来描述轴突内部的信号传导过程，这些信号传导过程组织内部信号，促进轴突对外部信号的反应能力。我们发现两种叫做Mud和zzzzed的蛋白质在这个过程中起作用。我们希望了解这些蛋白的确切作用机制，以及它们如何促进中枢神经系统轴突的靶向生长。我们知道，在哺乳动物神经系统的发育过程中，类似的分子也很活跃。通过使用果蝇，我们可以快速确定这些分子的作用机制，以及它们活动所必需的伙伴。此外，果蝇的使用使我们减少了在研究中牺牲大量小鼠的需要。一旦我们发现这些分子是如何在果蝇中起作用的，我们就会通知其他研究人员，以便在其他模型系统中测试这些分子。我们需要这些信息来了解神经系统是如何形成的，并找出哪些分子可能对帮助我们修复导致瘫痪或神经退化的神经损伤或疾病有用。不幸的是，哺乳动物不能修复发生在大脑中的神经损伤，我们的希望是，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 together 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 during 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 signal information into the axon to direct its growth. To enable this to happen efficiently the nerve cell has to co-ordinate its internal organisation with that of the external signals. By studying these processes we will understand better how the nervous system is formed and we can apply this knowledge to aiding the development of strategies to repair the nervous system of patients who have suffered neural injury or disease.We want to find the molecules that work to control the growth of the axon to guide it along its 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 the signalling processes that function within the axon to organise internal signals that facilitate the axon's ability to respond to external signals. We have found that two proteins called Mud and Frizzled have a role in this process. We wish to understand the precise mechanisms of action of these proteins and how they facilitate the targeted growth of axons in the central nervous system. We know that similar molecules are also active during the development of the mammalian nervous system. By using Drosophila we can rapidly identify the mechanims by which these molecules act and the partners that are necessary for their activity. Also use of Drosophila allows us to 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.