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

项目总结/摘要 项目负责人：Stephen Santoro 嗅觉感觉神经元对气味受体基因的选择如何决定其布线 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的位置 在嗅球内，依赖于单个特定的气味受体（OR）基因， OSN“选择”表达。这个过程的一个有趣的方面是OR蛋白本身 在OSN轴突的指导和完善中起着关键作用，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， 两个层次：首先，我们将测试我们已经确定的转录因子是 在OSN中以活性依赖性方式表达的蛋白质可能参与调节 介导OSN的活性依赖性引导和/或细化的基因的表达 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， 在OR依赖性轴突引导/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是否在轴突内被主动转运和翻译， 末端，在那里它们已经被证明是存在的，沿着OR蛋白。 此外，我们还将研究一组有趣的反义RNA在细胞凋亡中的潜在作用。 运输和/或调节轴突OR mRNA。该项目预计将有助于阐明 OSN对OR基因的选择决定了其活性依赖性连接。一般来说，这 这项工作有望为神经元活动如何指导神经元发育提供见解。 神经系统以及这些过程的中断如何导致神经系统疾病， 包括自闭症谱系障碍。

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.