TARGET FACULTY/NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们神经系统的细胞相隔很远，必须通过能够传输电信号或化学信号的线路相互连接。神经线的单个纤维被称为轴突，在早期胚胎中，它们必须经过很长的距离才能连接神经系统。了解它们用来导航的地标是什么，这不仅是为了了解我们的大脑是如何形成的，而且也是设计出刺激损伤后轴突重新生长的方法的起点，尤其是脊髓损伤。目前已知的导航线索很少，当然不足以解释我们大脑中连接的复杂性。这个子项目的重点是试图识别轴突用来感知线索的新线索和新受体。我们用果蝇作为模式生物，因为它有非常发达的遗传学。我们可以敲除单基因的功能，并观察是否出现导航错误。我们发现了一组我们特别感兴趣的单基因突变，并发现其中一些突变专门影响胚胎神经系统的连接模式。通过非常详细地分析突变对单个轴突的影响，我们相信我们已经发现了一种蛋白质，正在生长的轴突发现了它的吸引力，所以朝着它的来源生长。我们还相信，我们已经找到了轴突感受蛋白质的受体。我们目前正在使用组织培养细胞测试这些模型。如果我们的模型是正确的，遗传学和试管(体外)证据的结合将阐明我们的脊髓和大脑是如何形成的，并可能为治疗方法的开发开辟一条新的途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cells of our nervous system are separated by large distances and have to be connected to one another by wiring capable of carrying electrical or chemical signals. The individual fibers of the wiring are known as axons, and in the early embryo they have to navigate large distances to connect up the nervous system. Understanding what are the landmarks they use to navigate is of great interest, not only for understanding how our brains form, but also as a starting point to devise ways to stimulate the re-growth of axons after injury, especially spinal cord injuries. Very few navigational cues are currently known, certainly not enough to explain the complexity of connections in our brains. This subproject is focused on trying to identify novel cues and novel receptors that the axons use to sense the cues. We use the fruit fly as a model organism as it has very well developed genetics ¿ we can knock out the function of single genes and look to see if navigational errors are made. We identified a set of mutations in single genes that we are particularly interested in, and have found that some of these mutations specifically affect the wiring pattern of the embryonic nervous system. By analyzing in great detail the effect of the mutations on single axons, we believe we have found a protein that growing axons find attractive, so grow towards its source. We also believe we have found the receptor that the axon senses the protein with. We are currently testing these models using tissue culture cells. If our model is correct, the combination of genetic and test tube (in vitro) evidence will shed light on how our spinal cords and brains form, and potentially opens a new avenue for the development of therapies.