TARGET FACULTY/NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

轴突引导中的靶标/新型细胞外蛋白

• 批准号: 7381464
• 负责人: Thomas Kidd
• 金额: $ 18.81万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381464
• 关键词: TARGET; FACULTY; NOVEL; EXTRACELLULAR; PROTEINS

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们神经系统的细胞之间相隔很远，必须通过能够传递电信号或化学信号的线路相互连接。连接神经的单个纤维被称为轴突，在早期胚胎中，它们必须通过很长的距离连接神经系统。了解它们用来导航的地标是非常有趣的，不仅是为了了解我们的大脑是如何形成的，而且也是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新的线索和轴突用来感知线索的新受体。我们使用果蝇作为模式生物，因为它具有非常发达的遗传学，我们可以敲除单个基因的功能，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特别影响胚胎神经系统的布线模式。通过详细分析突变对单个轴突的影响，我们相信我们已经找到了一种蛋白质，生长的轴突会发现这种蛋白质的吸引力，因此会朝着它的来源生长。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，并可能为治疗的发展开辟一条新的途径。