Targeting of sensory axons in the olfactory bulb

描述(申请人提供)：这项提案的目标是了解嗅觉回路的第一个元素是如何在胚胎发育期间正确连接在一起的。嗅觉神经元将轴突从嗅觉上皮投射到大脑中的嗅球。值得注意的是，从散布在上皮中的神经元延伸出来的轴突，选择表达来自大量受体的相同气味受体，在球茎内特定的可重复位置汇聚在一起。这项研究建议解决嗅觉感觉轴突如何在大脑中定位其正确的目标。该项目利用斑马鱼胚胎的相对简单、快速发展和实验可及性的优势来研究感觉神经元的引导。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。气味感受器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得的初始阶段是重要的，还是在以后的阶段 感觉轴突结合成不同的神经毛结构，称为肾小球。第三个目的是解决一大类重要的轴突引导线索--信号素在嗅轴突靶向中的作用。这项工作将探索引导受体和嗅觉受体的表达是如何协调的，以及引导线索如何确定感觉轴突在灯泡中的目标位置。嗅觉神经元不断地诞生，并在成熟的嗅球内建立新的连接。了解这些连接是如何在发育过程中形成的，对于理解这一过程如何在神经退行性疾病中失败是至关重要的。

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.