Developing new Drosophila models to understand dystonia pathogenesis

Mutations in the ε-sarcoglycan gene cause DYT 11, a movement disorder with mostly early onset. ε-Scg is part of the mammalian sarcoglycan complex in muscles, but it has been shown to be more widely expressed than the other sarcoglycans, in particular in the brain. Thus far, very little is known about the neuronal function of epsilon sarcoglycan. In this project we will investigate the neuronal function of α/ε-Scg, the Drosophila homologue of ε-Scg. Drosophila was selected as a model organism, because it shows reduced functional redundancy for the sarcoglycan proteins. We will investigate the tissue-specific distribution of the protein in Drosophila, determine whether a neuronal sarcoglycan complex exists and if complex formation is conserved in invertebrates. To this end, we will compare the phenotypes of tissue-specific knockdown of epsilon sarcoglycan. In addition, we will analyse how the loss of α/ε-Scg impacts the nervous system. The phenotypes will be analysed in various assays to identify possible roles in the control of behaviour, and the physiology and formation of the nervous system. We will continue with performing appropriate screens (deficiency-, enhancer- or suppressor screens) to find neuronal interaction partners of α/ε-Scg. At the conclusion of the project, we expect to have identified and characterized the role of α/ε- Scg in neuronal function and development in Drosophila, which may ultimately identify new approaches in treating Dystonia.

Publication year:2021

Accessibility:Open