Targeting of sensory axons in the olfactory bulb

项目摘要/摘要 这项建议的目标是了解嗅觉回路的第一个元素是如何正确连接的 在胚胎发育期间聚在一起。嗅觉神经元从嗅觉上皮投射轴突 连接到大脑中的嗅球。上皮中的每个嗅觉感觉神经元选择一种气味 受体从一个非常大的基因库中表达。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汇聚在一起的特定可重复的延伸轴突 嗅球内的位置。这项研究提案阐述了嗅觉感觉轴突是如何如此精确地 在大脑中定位它们的特定目标。这个项目利用了斑马鱼相对简单的优势。 嗅觉系统及其发育和实验可达性研究感觉引导 嗅觉上皮和嗅球之间的神经元。在第一个目标中，假设转录因子 协调指导特定气味受体和轴突引导受体的表达将被测试。 这应该有助于确定某些气味受体和引导受体是如何表达的 在相同的感觉神经元中。在第二和第三个目标中，轴突引导分子引导 将识别嗅觉感觉神经元在嗅球中的特定靶点的轴突，并 以突变胚胎为特征的。到目前为止，这个项目已经确定了12个信号蛋白，它们参与了 嗅觉轴突引导。随着这个项目识别出更多的引导分子，它们的特异性 将详细研究在选择性分束、轴突分支选择和靶场识别中的功能。 这些研究正在建立一个系统层面的理解如何组装一个重要的功能电路 在开发过程中。这一知识将在制定再生和治疗方法时至关重要。 嗅觉障碍患者的嗅觉回路修复。

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.