Analysis of glial impact on larval locomotion in Drosophila

• Applicant: Professor Dr. Christian Klämbt
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 385967980

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.

• DFG Programme: Research Grants