Analysis of glial impact on larval locomotion in Drosophila

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，而包膜神经胶质细胞代谢支持和隔离神经元突起。为了系统地揭示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，并确定了Shopper，一种由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，出现了一种独特的幼虫运动表型，包括更高水平的头部弯曲以及更低的蠕动效率和频率。我们发现，表达包鞘胶质细胞的购物者有助于谷氨酸稳态，尽管它们缺乏与突触的任何特定接触，现在将解决购物者控制幼虫运动的神经元。哺乳动物亚硫酸盐氧化酶(SUOX)也由少突胶质细胞高表达，SUOX的缺失会导致严重的神经功能障碍。此外，我们还设计了一种新的方法来具体破译胶质细胞在调节神经元网络功能中的作用，并鉴定了其功能将被解剖的胶质谷氨酸受体。正如果蝇购物者和人类suox突变表型之间惊人的相似之处所突显的那样，我们希望能够阐明哺乳动物神经胶质细胞的相似特性。

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.