Targeting of sensory axons in the olfactory bulb

描述（由申请人提供）：本提案的目的是了解嗅觉回路的第一个元素是如何在胚胎发育过程中正确连接在一起的。嗅觉神经元将轴突从嗅上皮投射到大脑中的嗅球。值得注意的是，从分散在上皮细胞中的神经元延伸出来的轴突，从大量的受体中选择表达相同的气味受体，在灯泡内的特定可重复位置聚集在一起。这项研究计划解决了嗅觉感觉轴突如何在大脑中定位正确的目标。该项目利用胚胎斑马鱼的相对简单，快速发展和实验可及性来研究感觉神经元的指导。在第一个目标中，我们将把气味受体的表达与灯泡内的目标位置联系起来。气味受体参与嗅觉感觉轴突的引导，第二个目的是检查它们的贡献在目标获取的初始阶段或以后的过程中是否重要。 感觉轴突合并成称为肾小球的不同的神经纤毛结构。第三个目标解决了一个大的和重要的一类轴突的指导线索，信号蛋白，嗅觉轴突靶向的作用。这项工作将探讨如何指导受体和嗅觉受体的表达是协调的，以及如何指导线索确定在灯泡的感觉轴突的目标位置。嗅感觉神经元不断地在成熟的嗅球内产生和建立新的连接。了解这些连接在发育过程中是如何形成的，对于了解这一过程在神经退行性疾病中是如何失败的至关重要。

DESCRIPTION (provided by applicant): 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.