Targeting of sensory axons in the olfactory bulb

项目总结/摘要 这个建议的目的是了解嗅觉回路的第一个元素是如何正确连接的 在胚胎发育过程中。嗅觉神经元从嗅上皮投射轴突 大脑中的嗅球上皮细胞中的每个嗅觉感觉神经元选择一种气味 从一个非常大的基因库表达受体。值得注意的是，所有的感觉神经元， 选择相同的气味受体来表达延伸的轴突，这些轴突以特定的可重复的方式聚集在一起， 在嗅球内的位置。这项研究计划解决了嗅觉感觉轴突如何如此精确地 在大脑中定位特定目标。这个项目利用了斑马鱼相对简单的特点 嗅觉系统及其发展和实验的可达性，以研究感官的指导 嗅上皮和嗅球之间的神经元。在第一个目标中，假设转录因子 将测试协同指导特定气味受体和轴突导向受体的表达。 这将有助于确定某些气味受体和引导受体的表达方式 在同一个感觉神经元中。在第二个和第三个目的中，指导神经元的轴突引导分子， 将识别嗅球中嗅觉感觉神经元至其特定靶点的轴突， 以突变的胚胎为特征。到目前为止，该项目已经确定了12个信号蛋白，有助于 嗅觉感觉轴突引导。随着该项目识别出更多的指导分子，它们的特异性 将详细研究选择性成束、轴突分支选择和目标区域识别中的功能。 这些研究正在建立一个系统级的理解如何组装一个重要的功能电路 在发展过程中。这方面的知识将是必不可少的，在制定治疗的再生和 嗅觉缺失患者嗅觉回路的修复。

PROJECT SUMMARY/ABSTRACT The objective of this proposal is to understand how the first elements of olfactory circuitry are correctly wired together during embryonic development. Odorant sensing neurons project axons from the olfactory epithelium to the olfactory bulb in the brain. Each olfactory sensory neuron in the epithelium chooses a single odorant receptor to express from a very large gene repertoire. Remarkably, all of the sensory neurons that have chosen the same odorant receptor to express extend axons that converge together in specific reproducible locations within the olfactory bulb. This research proposal addresses how olfactory sensory axons so precisely locate their specific targets in the brain. This project takes advantage of the relative simplicity of the zebrafish olfactory system and its developmental and experimental accessibility to study the guidance of sensory neurons between the olfactory epithelium and the bulb. In the first aim, the hypothesis that transcription factors coordinately direct the expression of particular odorant receptors and axonal guidance receptors will be tested. This should help determine how certain groups of odorant receptors and guidance receptors are expressed together in the same sensory neurons. In the second and third Aims, axonal guidance molecules that direct the axons of olfactory sensory neurons to their specific targets in the olfactory bulb will be identified and characterized in mutant embryos. Thus far, this project has identified 12 signaling proteins that contribute to olfactory sensory axon guidance. As this project identifies additional guidance molecules, their specific functions in selective fasciculation, axon branch selection, and target field recognition will be studied in detail. These studies are building a systems level understanding of how an important functional circuit is assembled during development. This knowledge will be essential in the formulation of therapies for the regeneration and repair of olfactory circuitry in anosmic patients.