Analysis of glial impact on larval locomotion in Drosophila

胶质细胞对果蝇幼虫运动的影响分析

• 批准号: 385967980
• 负责人: Professor Dr. Christian Klämbt
• 金额: --
• 依托单位: Institut für Neuro- und Verhaltensbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/385967980?language=en
• 关键词: Analysis; glial; impact; larval; locomotion

In all complex nervous systems, neurons are accompanied by glial cells. Astrocytes are known to modulate synaptic function whereas ensheathing glial cells metabolically support and insulate neuronal processes. To systematically unravel the role of glial cells during neuronal network function we performed a glial specific RNAi screen in Drosophila and identified shopper, a sulfite oxidase specifically expressed by the ensheathing glia. In shopper mutants, a distinct larval locomotion phenotype develops, comprising elevated levels of head bending as well as reduced peristalsis efficiency and frequency. We found that shopper expressing ensheathing glial cells contribute to glutamate homeostasis despite the fact that they lack any specific contact to synapses and will now address on which neurons shopper acts to control larval locomotion. The mammalian Sulfite oxidase (SUOX) is also highly expressed by oligodendrocytes, and loss of suox leads to severe neurological deficits. In addition, we have devised a novel approach to specifically decipher the glial contribution in modulating neuronal network function and identified glial glutamate receptors whose function will be dissected. As highlighted by the striking similarities between Drosophila shopper and human suox mutant phenotypes, we expect to shed light on similar properties of mammalian glia.

在所有复杂的神经系统中，神经元都伴随着神经胶质细胞。已知星形胶质细胞调节突触功能，而成鞘胶质细胞代谢支持和隔离神经元过程。为了系统地阐明神经胶质细胞在神经元网络功能中的作用，我们在果蝇中进行了胶质细胞特异性RNAi筛选，并鉴定了shopper，一种由成鞘胶质细胞特异性表达的亚硫酸盐氧化酶。在购物者突变体中，形成了一种独特的幼虫运动表型，包括头部弯曲水平升高以及寄生效率和频率降低。我们发现，购物者表达成鞘神经胶质细胞有助于谷氨酸稳态，尽管事实上，他们缺乏任何特定的接触突触，现在将解决哪些神经元购物者的行为来控制幼虫的运动。哺乳动物亚硫酸盐氧化酶（SUOX）也由少突胶质细胞高度表达，并且suox的缺失导致严重的神经功能缺损。此外，我们还设计了一种新的方法来专门破译神经胶质细胞在调节神经元网络功能中的贡献，并确定了神经胶质细胞谷氨酸受体，其功能将被解剖。正如果蝇购物者和人类suox突变表型之间惊人的相似性所强调的那样，我们希望阐明哺乳动物神经胶质的相似特性。