The effect of survival motor neuron deficiency on motor function in Drosophila

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results from mutations present within the survival of motor neuron (SMN) gene. SMA is caused by a quantitative reduction (not total absence) of SMN protein. In humans, the SMN complex is an essential multi-protein molecule composed of an integral SMN protein, Gemins 2-8 and Unrip, which is crucial for small nuclear ribonucleoproteins (snRNP) assembly. In the present study, the SMN protein was studied using the model organism Drosophila melanogaster. The fly has been successfully used in the study of many neurodegenerative diseases, particularly due to human gene homologues and conserved neuromuscular physiology. With the use of three different SMN mutations, SMA was modelled by creating fly genotypes which were assessed for neuromuscular degeneration. The fly genotypes that were generated were subjected to a battery of behavioural tests which included locomotor and flight ability assays. Neuromuscular dysfunction presenting as flight defects were seen in mutant flies, as well as reduced lifespan. We also tested the role of SMN on adult viability by selectively decreasing expression levels of SMN in different tissues. Our results showed that SMN deprivation within glial cells results in total fly lethality. These findings show that different SMN mutations cause significant effects on motor function and that SMN has both a tissue-specific and ubiquitous role in Drosophila, beginning at even the primal stages of development. Together, these characteristics influence the formation of the SMN complex, its function and allow us to further understand the molecular pathogenesis of SMA.