Molecular basis of specification and connectivity of sensory neurons in the olfactory system of Drosophila melanogaster

果蝇嗅觉系统感觉神经元规范和连接的分子基础

• 批准号: 66639291
• 负责人: Professorin Dr. Ilona Grunwald Kadow
• 金额: --
• 依托单位: Institut für Physiologie II
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/66639291?language=en
• 关键词: Molecular; basis; specification; connectivity; sensory

The olfactory system discriminates between a large number of odorants using precisely wired projections from neurons in the periphery to neurons in higher brain centers. The ability to respond to an odor is instrumental in driving important behaviors. Olfactory receptor neurons (ORN) express specific receptors and neurons expressing one receptor class innervate the same substructures called glomeruli in the brain. The olfactory system of the fruitfly Drosophila melanogaster exhibits a highly similar organization to the mammalian olfactory system. Its genetic tractability makes it an ideal model to study how this striking specificity in neuron identity and corresponding wiring is achieved. My future research aims at understanding how ORN specificity and connectivity are coordinated genetically, and at identifying the molecular mechanisms that ultimately allow the construction of a functional neuronal network. It is conceivable that the ochestration of specification and connectivity is provided by ORN class specific molecules such as transcription factors. I am proposing two main approaches to find the critical regulators in this process: (1) previously identified mutants from my postdoctoral work showing neuron specification phenotypes and striking connectivity mutants will be analyzed, and (2) in order to discover the neuron-specific transcription factors and the transmembrane receptors that govern class specific wiring, candidate gene groups will be analyzed using overexpression of inhibitory RNA. In an independent approach directly following up my previous work, the function of the FGF receptor Breathless in one specific ORN class will be characterized.

嗅觉系统利用从外围神经元到高级大脑中心神经元的精确连线投射来区分大量的气味。对气味作出反应的能力有助于推动重要的行为。嗅觉受体神经元（ORN）表达特定的受体，表达一种受体的神经元支配大脑中称为肾小球的相同亚结构。果蝇（Drosophila melanogaster）的嗅觉系统与哺乳动物的嗅觉系统具有高度相似的结构。它的遗传易处理性使其成为研究神经元身份和相应布线中这种惊人特异性是如何实现的理想模型。我未来的研究旨在了解ORN特异性和连接性如何在遗传上协调，并确定最终允许构建功能性神经元网络的分子机制。可以想象的是，通过ORN类特异性分子如转录因子来提供特异性和连接性的表现。我提出了两个主要的方法来找到这个过程中的关键调节器：（1）以前从我的博士后工作中发现的突变体显示神经元特异性表型和显着的连接突变体将被分析，（2）为了发现神经元特异性转录因子和跨膜受体，管理类特异性布线，候选基因组将使用抑制性RNA的过表达进行分析。在一个独立的方法直接跟进我以前的工作，FGF受体Breathless在一个特定的ORN类的功能将被表征。

项目成果

Drosophila Psidin Regulates Olfactory Neuron Number and Axon Targeting through Two Distinct Molecular Mechanisms

果蝇 Psidin 通过两种不同的分子机制调节嗅觉神经元数量和轴突靶向

• DOI: 10.1523/jneurosci.3116-12.2012
• 发表时间: 2012
• 期刊: The Journal of Neuroscience
• 作者: Stephan;Sanchez-Soriano;Loschek;Gerhards;Gutmann;Storchova;Prokop;Grunwald Kadow
• 通讯作者: Grunwald Kadow