MOLECULAR BASIS OF CONVERGENCE BY OLFACTORY NEURONS

嗅觉系统如何辨别气味在很大程度上是未知的。 生理学研究表明，嗅觉神经元具有类似的 功能特异性投射到嗅觉中的相同肾小球， 灯泡 1000个或更多广泛分散的神经元在一个 单个肾小球代表了令人印象深刻的分类程度， 面向. 什么样的分子线索引导生长锥进入和进入 灯泡？ 为了识别这些信号，斑马鱼胚胎将被用作模型 系统，因为它的解剖简单性和光学清晰度。 两 使用单克隆抗体或RNA原位进行简单筛选 杂交技术，将用于寻找分子， 表达仅限于球部，鼻上皮， 和/或轴突。 这些潜在的寻路或 目标候选人将被隔离，并进行一般功能测试 错误表达实验 一个非常有希望的目标 分子已经在人类和鸡中被鉴定。 当突变时， 这种基因导致卡尔曼综合征，一种特征为 由于嗅觉神经元不能支配嗅球而引起的嗅觉丧失。 这项提议将试图克隆斑马鱼的同源基因， 在这个解剖学上简单的系统中研究它。

How the olfactory system discriminates among odorants is largely unknown. Physiological studies suggest that olfactory neurons with similar functional specificities project to the same glomerulus in the olfactory bulb. The convergence of 1000 or more widely dispersed neurons on a single glomerulus represents an impressive degree of sorting and targeting. What molecular cues guide growth cones to and within the bulb? To identify these signals, the zebrafish embryo will be used as a model system because of its anatomical simplicity and optical clarity. Two simple screens, using either a monoclonal antibody or an RNA in situ hybridization technique, will be employed to search for molecules whose expression is restricted to subsets of the bulb, the nasal epithelium, and/or the axons during development. These potential pathfinding or targeting candidates will be isolated, and functionally tested in general misexpression experiments. One highly promising putative targeting molecule has already been identified in human and chick. When mutant, this gene results in Kallmann's Syndrome, a defect characterized by anosmia due to a failure of olfactory neurons to innervate the bulb. This proposal will attempt to clone the zebrafish homolog in order to study it in this anatomically simple system.