Transcriptome Analysis of Neuronal and Muscle Tissue in Smn Mutant Drosophila melanogaster

Abstract

Spinal muscular atrophy (SMA) is a devastating human neurodegenerative disease caused by a defect in the gene SMN1 resulting in a loss of the protein Survival Motor Neuron (SMN). The model organism Drosophila melanogaster has a conserved homologue of the human SMN1 gene, Smn, and its knockdown produces SMA-like phenotypes. SMN’s role in the cell is not fully understood; despite being ubiquitous and cell lethal it appears to target motor neurons in the SMA disease phenotype, suggesting tissue specific function. This study investigates the tissue-specificity of Smn function and its role in Drosophila muscle and neuronal tissue. We used RNA-Seq analysis of muscle and CNS to investigate transcriptome changes when Smn is knocked down in a model that mimics the human SMA phenotype. We found many differentially expressed genes and changes in differential exon usage. We explored the enriched GO terms and KEGG pathways associated with the gene sets from each respective tissue. To further investigate Smn’s role in the muscle we demonstrated a dose-dependent model of SMA and found a set of genes whose expression profiles are correlated with the amount of Smn present in the tissue. We compared our results from each tissue to what is currently known about SMN and to our lab’s previous findings. Our results show that many aspects of Smn’s role in the cell are tissue-specific; each tissue shows distinct differentially expressed genes and differentially used exons. Not only are the genes themselves tissue-specific but the significantly enriched biological processes and pathways associated with them were as well.