MOLECULAR BASIS OF CONVERGENCE BY OLFACTORY NEURONS

嗅觉系统如何区分气味剂在很大程度上尚不清楚。 生理学研究表明，嗅觉神经元具有相似的功能 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汇聚在一个 单个肾小球代表了令人印象深刻的分类和 瞄准。 什么分子线索引导生长锥进入并在其中 灯泡？ 为了识别这些信号，将使用斑马鱼胚胎作为模型 系统因其解剖结构简单且光学清晰。 两个 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具有以下性质的分子： 表达仅限于球部、鼻上皮、 和/或发育期间的轴突。 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。 一种非常有前途的假定目标 该分子已在人类和小鸡体内得到鉴定。 当突变时， 该基因导致卡尔曼综合症，这是一种缺陷，其特征是 由于嗅觉神经元无法支配灯泡而导致的嗅觉丧失。 该提案将尝试克隆斑马鱼同源物，以便 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.