Project 1: how an olfactory sensory neuron's choice of ordorant receptor gene determines its wiring

项目1：嗅觉感觉神经元对气味受体基因的选择如何决定其接线

• 批准号: 9210802
• 负责人: Stephen Santoro
• 金额: $ 20.95万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9210802
• 关键词: Active Biological Transport; Antisense RNA; Axon; Axonal Transport; Biochemical; Bioinformatics; Biology; Centers of Research Excellence; Defect; Dendrites; Development; Event; Gene Expression; Genes; Genetic Transcription; Genetic Translation; Genome; Lead; Ligands; Link; Location; Mammals; Maps; Mediating; Messenger RNA; Molecular; Mus; Mutant Strains Mice; Nervous system structure; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurons; Odorant Receptors; Olfactory Pathways; Play; Process; Protein Biosynthesis; Proteins; Receptor Gene; Regulation; Regulator Genes; Role; Sensory; Signal Pathway; Signal Transduction; Testing; Transgenic Organisms; Translating; Translations; Untranslated RNA; Work; Wyoming; autism spectrum disorder; axon guidance; base; experimental study; fascinate; gene function; insight; nervous system development; nervous system disorder; olfactory bulb; olfactory sensory neurons; relating to nervous system; theories; transcription factor

Project Summary/Abstract Project Lead: Stephen Santoro   How an olfactory sensory neuron's choice of odorant receptor gene determines its wiring In mammals, each olfactory sensory neuron (OSN) projects a single axon to a precise location within the olfactory bulb that depends on the single specific odorant receptor (OR) gene that the OSN `chooses' to express. A fascinating aspect of this process is that the OR protein itself plays a critical role in the guidance and refinement of the OSN axon, in part through its level of signaling activity. How OR activity regulates the expression of molecules required for the precise guidance and refinement of axons is largely unknown. We propose to study this phenomenon on two levels: First, we will test the hypothesis that transcription factors that we have identified to be expressed in an activity-dependent manner in OSNs may be involved in regulating the expression of genes that mediate the activity-dependent guidance and/or refinement of OSN axons. Second, we will use two transgenic approaches to characterize the role of axonal mRNA transport and translation in OR-dependent axon guidance/refinement. As part of this objective, we will investigate whether OR mRNAs are actively transported and translated within axon termini, where they have previously been shown to be present, along with OR proteins. Moreover, we will investigate a potential role for an intriguing set of antisense RNAs in the transport and/or regulation axonal OR mRNAs. This project is expected to help elucidate how an OSN's choice of OR gene determines its activity-dependent connectivity. More generally, this work is expected to provide insights into how neuronal activity guides the development of the nervous system and how disruption of these processes contribute neurological disorders, including autism spectrum disorders.

项目概要/摘要 项目负责人：斯蒂芬·桑托罗   嗅觉感觉神经元对气味受体基因的选择如何决定其接线 在哺乳动物中，每个嗅觉感觉神经元 (OSN) 将单个轴突投射到精确位置 嗅球内的气味依赖于单个特定的气味受体（OR）基因， OSN“选择”来表达。这个过程的一个令人着迷的方面是 OR 蛋白本身发挥着 在 OSN 轴突的指导和完善中发挥着关键作用，部分是通过其水平 信号活动。 OR活性如何调节精确表达所需分子的表达 轴突的引导和细化在很大程度上是未知的。我们建议研究这一现象 两个层面：首先，我们将检验我们已经确定的转录因子的假设 OSNs 中以活性依赖性方式表达可能参与调节 介导 OSN 活动依赖性指导和/或细化的基因表达 轴突。其次，我们将使用两种转基因方法来表征轴突 mRNA 的作用 OR 依赖的轴突引导/细化中的运输和翻译。作为这一目标的一部分， 我们将研究 OR mRNA 是否在轴突内主动运输和翻译 末端，之前已证明它们与 OR 蛋白一起存在。 此外，我们将研究一组有趣的反义 RNA 在 运输和/或调节轴突或mRNA。该项目预计将有助于阐明如何 OSN 对 OR 基因的选择决定了其活性依赖性连接。更一般地说，这 预计这项工作将提供关于神经元活动如何指导发育的见解 神经系统以及这些过程的破坏如何导致神经系统疾病， 包括自闭症谱系障碍。