Whole transcriptome analysis of a reversible neurodegenerative process in Drosophila reveals potential neuroprotective genes

ABSTRACT: Background. Neurodegenerative diseases are progressive and irreversible and they can be originated by mutations in specific genes. Spalt-like genes (Sall) encode transcription factors expressed in the central nervous system. In humans, SALL mutations are associated with hereditary syndromes characterized by mental retardation, sensorineural deafness and motoneuron problems, among others. Drosophila sall mutants exhibit severe neurodegeneration of the Central Nervous System, which surprisingly reverts later in development, suggesting a potential to recover from neurodegeneration. We hypothesize that this recovery is mediated by a reorganization of the transcriptome counteracting SALL lost. To identify genes associated to neurodegeneration and neuroprotection, we used mRNA-Seq to compare the transcriptome of Drosophila sall mutant and wild type embryos from neurodegeneration and reversal stages. Results. Neurodegeneration stage is temporally associated with transcriptional changes in 220 genes, of which only 5% were already described as relevant for neurodegeneration. Genes related to the groups of Redox, Lifespan/Aging and Mitochondrial diseases are significantly represented at this stage. By contrast, neurodegeneration reversal stage is associated with significant changes in 480 genes, including 424 not previously associated with neuroprotection. Immune response and Salt stress are the most represented groups at this stage. We validated our result by comparison with data from modENCODE project and by Quantitative PCR. Conclusions. We identify new genes associated to neurodegeneration and neuroprotection by using an mRNA-Seq approach. The strong homology between Drosophila and human genes raises the possibility to unveil novel genes involved in neurodegeneration and neuroprotection also in humans. Key words: mRNA-Seq, spalt, SALL, Neurodegeneration, Neuroprotection, Drosophila

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE38664 | GEO | 2012/11/07

SECONDARY ACCESSION(S): PRJNA168361

REPOSITORIES: GEO