Characterization of novel Drosophila candidate axon guidance molecules

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。我们希望找到作为这些受体或信号的分子，引导轴突沿着它们的路径前进。据我们所知，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，如果蝇，它们做同样的工作，但规模更小。然而，我们也知道，我们还没有找到连接神经系统所需的所有分子。为了寻找更多的分子，我们在老鼠、人类和果蝇的基因组中进行了搜索，以找到彼此相似的分子，以及那些我们已经知道的在发育中的神经系统中发现的分子。我们计划用果蝇作为一个模型系统，在那里我们可以干扰或移除这些新分子的功能，以找出它们是否以及如何起到指导神经生长的作用。我们使用果蝇作为模型系统，这样我们就可以快速测试这些新分子的作用，并允许我们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. We want to find the molecules that work as these receptors or cues to guide axons along their pathways. From what we know already 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. However we also know we haven't found all the molecules needed to wire-up the nervous system. To find additional molecules we have searched through the genomes of mouse, human and Drosophila to find molecules that are similar to one another and to those we already know about which are found in the developing nervous system. We plan to use Drosophila as a model system where we can disrupt or remove the function of these new molecules to find out if and how they act to direct nerve growth. We use Drosophila as a model system so we can rapidly test the role of these new molecules and to allow 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.