Odorants, Receptors and Glomeruli

气味剂、受体和肾小球

基本信息

批准号：
7235262
负责人：
Charles A Greer
金额：
$ 81.61万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7235262
关键词：
Adenovirus Vector Adult Afferent Neurons Anatomy Axon Back Basic Science Biological Models Biopsy Classification Code Collaborations Contracts Data Development Epithelial Epithelium Family Fluorescence Funding Funding Mechanisms Gene Targeting Genetic Genomics Geographic Distribution In Situ Hybridization Joints Laboratories Leadership Literature Maps Molecular Biology Mus Mutagenesis Mutation Neighborhoods Neurons Numbers Odorant Receptors Olfactory Epithelium Olfactory Nerve Paper Pattern Physiology Population Positioning Attribute Publishing Reagent Receptor Gene Research Research Personnel Research Project Grants Resources Site Sorting - Cell Movement Spatial Distribution Staging System Testing Time Universities Work base hyposmia innovation insight interdisciplinary approach isovaleric acid member mouse genome neural circuit neuronal cell body olfactory bulb programs receptor expression research study response

项目摘要

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发育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) 表达小鼠基因组中大约 1000 个完整的气味受体 (OR) 基因之一。表达给定 OR 基因的 OSN 细胞体分散在嗅觉上皮内的四个区域之一，并且它们的轴突汇聚到小鼠嗅球中约 1800 个肾小球中的几个上。因此提出了一个映射问题：必须将 1000 个 OSN 群体（每个群体表达不同的 OR）分类到大约 1800 个肾小球上。什么定义了表达特定 OR 或响应特定气味的 OSN 轴突在球茎中汇聚的位置？我们对定义肾小球位置的参数的理解进展缓慢。尚未对肾小球阵列进行系统研究，并且文献分散于物种、气味剂、OR 和肾小球之间。研究肾小球会聚的一种有效方法是 OR 基因的定向诱变，以在表达给定 OR 基因的 OSN 中表达轴突标记。这些实验表明，OR 是轴突会聚到肾小球的关键决定因素。在这里，我们提出了一种以小鼠为中心、基于 OR 和肾小球有意义的子集的协调、系统的方法。该方法是分子生物学和遗传学、生理学和解剖学的综合结合。我们的假设是，定义小鼠嗅球肾小球阵列中邻域的参数是：OR 序列特征、气味反应性以及 OR 表达的起始点和区域。具体目标 1：如何根据气味受体序列和气味反应性定义邻近肾小球？具体目标 2：已知基因组位点上两个相关 OR 基因家族的肾小球组织是怎样的？具体目标 3：OR 表达的时间和区域与肾小球位置有何关系？