Odorants, Receptors and Glomeruli

气味剂、受体和肾小球

• 批准号: 6895499
• 负责人: PETER MOMBAERTS
• 金额: $ 77.4万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895499
• 关键词: axon; biological models; brain mapping; chemoreceptors; functional /structural genomics; green fluorescent proteins; in situ hybridization; laboratory mouse; molecular cloning; northern blottings; nucleic acid sequence; olfactions; olfactory lobe; polymerase chain reaction; receptor expression

DESCRIPTION (provided by applicant): The mammalian olfactory system is increasingly recognized as an attractive model system for studying the formation of neural circuits during development. An olfactory sensory neuron (OSN) expresses one the of approximately 1000 intact odorant receptor (OR) genes in the mouse genome. Cell bodies of OSNs expressing a given OR gene are dispersed in one of four zones within the olfactory epithelium, and their axons converge onto a few of the approximately 1800 glomeruli in the olfactory bulb of the mouse. A mapping problem is thus posed: 1000 populations of OSNs, each expressing a distinct OR, must be sorted onto approximately 1800 glomeruli. What defines the site in the bulb to which axons of OSNs expressing a given OR or responding to given odorants converge? Progress in our understanding of the parameters defining glomerular position has been slow. No systematic studies of the glomerular array have been undertaken, and the literature is fragmented across species, odorants, ORs and glomeruli. A productive approach to study glomerular convergence has been targeted mutagenesis of OR genes to express axonal markers in OSNs expressing a given OR gene. Such experiments have revealed that the OR is a critical determinant of axonal convergence to glomeruli. Here we propose a coordinated, systematic approach focusing on the mouse and based on meaningful subsets of ORs and glomeruli. The approach is an integrated combination of molecular biology and genetics, physiology, and anatomy. Our hypothesis is that parameters defining a neighborhood in the glomerular array of the mouse olfactory bulb are: OR sequence features, odorant responsiveness and onset and zone of OR expression. Specific Aim 1: How are neighboring glomeruli defined in terms of odorant receptor sequence and odorant responsiveness? Specific Aim 2: What is the glomerular organization of two families of related OR genes at a known genomic locus? Specific Aim 3: How are time and zone of OR expression related to glomerular position?

描述（由申请人提供）：哺乳动物嗅觉系统越来越被认为是研究开发过程中神经回路形成的有吸引力的模型系统。嗅觉感觉神经元（OSN）表示小鼠基因组中约1000个完整的气味受体（OR）基因的一种。表达给定基因或基因的OSN的细胞体分散在嗅觉上皮的四个区域之一中，其轴突在小鼠的嗅球中收集到大约1800个肾小球中的一些。因此提出了一个映射问题：1000个OSN种群，每个OSN都必须在大约1800个肾小球上排序。是什么定义了灯泡中的位点，以表达给定的气味的OSN轴突汇聚？我们对定义肾小球位置的参数的理解的进展一直很慢。尚未对肾小球阵列进行系统的研究，并且文献跨物种，气味剂和肾小球分散。研究肾小球收敛的生产方法已被靶向或基因的诱变，以表达表达给定基因的OSN中的轴突标记。这样的实验表明，OR是轴突收敛到肾小球的关键决定因素。在这里，我们提出了一种协调的，系统的方法，重点是小鼠，并基于有意义的ORS和glomeruli子集。该方法是分子生物学和遗传学，生理学和解剖结构的综合组合。我们的假设是，在小鼠嗅球的肾小球阵列中定义邻域的参数是：或序列特征，气味响应能力以及发作和或表达区域。特定目标1：如何根据气味受体序列和气味反应性定义相邻的肾小球？特定目的2：两个相关基因或基因家族的肾小球组织是什么？特定目标3：与肾小球位置有关的时代和区域或表达如何？