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。值得注意的是，从散布在脑内的神经元延伸出来的轴突 上皮细胞，但选择表达来自大量受体的相同气味受体，汇聚 一起在球茎内的特定可复制位置。这项研究提案阐述了嗅觉是如何 感觉轴突在大脑中定位其正确的目标。该项目利用了相对简单的优势， 快速发展，并实验可及性的胚胎斑马鱼研究的感官指导 神经元。在第一个目标中，我们将气味受体的表达与球茎内的目标位置联系起来。臭味剂 受体参与嗅觉感觉轴突的引导，第二个目的是检查它们的 在目标获得的初始阶段或以后，当感觉神经轴突结合成 不同的神经毛结构称为肾小球。第三个目标涉及一个大而重要的班级的作用 在嗅觉轴突靶向的轴突引导线索中，信号素。这项工作将探索如何指导 受体和嗅觉受体的表达是协调的，以及引导线索如何确定目标 感觉轴突在球部的位置。嗅觉感觉神经元不断地诞生和制造新的 成熟嗅球内的连接。了解这些连接在开发过程中是如何形成的 将是理解这一过程如何在神经退行性疾病中失败的关键。

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. Remarkably, axons extending from neurons that are scattered in the epithelium but choose to express the same odorant receptor from a large repertoire of receptors, converge together in specific reproducible locations within the bulb. This research proposal addresses how olfactory sensory axons locate their correct targets in the brain. The project takes advantage of the relative simplicity, rapid development, and experimental accessibility of the embryonic zebrafish to study the guidance of sensory neurons. In the first aim we will relate odorant receptor expression to target location within the bulb. Odorant receptors participate in the guidance of olfactory sensory axons and the second aim examines whether their contribution is important during the initial stages of target acquisition or later as sensory axons coalesce into distinct neuropilar structures called glomeruli. The third aim addresses the role of a large and important class of axonal guidance cues, the semaphorins, in olfactory axon targeting. This work will explore how guidance receptors and olfactory receptor expression is coordinated, and how guidance cues determine the target locations of sensory axons in the bulb. Olfactory sensory neurons are constantly being born and making new connections within the mature olfactory bulb. Understanding how these connections form during development will be essential in understanding how this process fails in neurodegenerative diseases.