ANALYSIS OF TRANSCIPTOME AND SPLICING CHANGES IN ZEBRAFISH MODEL FOR SPINAL MUSCULAR ATROPHY

Abstract

Spinal Muscular Atrophy (SMA) is a human neurodegenerative disease that leads to motor neuron loss and paralysis. SMA is caused by reduced levels of the ubiquitously expressed protein, Survival Motor Neuron (SMN). It remains unclear how a SMN deficiency leads to an apparently motor neuron specific phenotype and whether other cell types are also involved in SMA pathology. In this study, I applied RNA sequencing to analyse the transcriptomes of motor neurons and Schwann cells in a zebrafish SMA model. I identified transcripts that are alternatively spliced in both cell types and are implicated in the maintenance of neuronal function. CRISPR/Cas was used to functionally characterize the most promising candidate identified by RNAseq. Taken together, I propose that SMN deficiency causes transcriptomic changes and altered splicing in motor neurons and Schwann cells that affects their physiology, and that Schwann cells might contribute to SMA pathology in a non-cell autonomous manner.