TARGET FACULTY/NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们神经系统的细胞相距很远，必须通过能够传递电信号或化学信号的线路相互连接。神经线路的单个纤维被称为轴突，在早期胚胎中，它们必须穿越很远的距离来连接神经系统。了解它们用来导航的标志是非常有趣的，不仅对理解我们的大脑是如何形成的，而且作为设计刺激损伤后轴突再生的方法的起点，特别是脊髓损伤。目前已知的导航线索非常少，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新的线索和新的受体，轴突用来感知线索。我们使用果蝇作为模型生物，因为它具有非常发达的基因，我们可以敲除单个基因的功能，看看是否会产生导航错误。我们在单个基因中发现了一系列我们特别感兴趣的突变，并发现其中一些突变特别影响胚胎神经系统的连接模式。通过详细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，生长中的轴突发现这种蛋白质很有吸引力，因此向它的来源生长。我们也相信我们已经发现了轴突感知蛋白质的受体。我们目前正在用组织培养细胞测试这些模型。如果我们的模型是正确的，基因和试管（体外）证据的结合将揭示我们的脊髓和大脑是如何形成的，并有可能为治疗的发展开辟一条新的途径。

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.