Date of Submission

Spring 2024

Academic Program

Biology

Project Advisor 1

Michael Tibbetts

Project Advisor 2

Brooke Jude

Abstract/Artist's Statement

MEGF10 is a gene involved in skeletal muscle regeneration; it is required for preserving myogenic precursors that regenerate skeletal muscle after injury. MEGF10 myopathy – also known as early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) – is a rare, life-threatening, and currently, incurable muscle disease caused by an autosomal recessive mutation in MEGF10. Recent findings have shown some interaction between Megf10 and Notch1 – a central receptor in the Notch signaling pathway, vital for skeletal muscle development. To understand the disease mechanism and explore potential therapies, I examined the consequences of deleting MEGF10's ortholog, Draper (Drpr)-/-, on the motor function of larvae and adult male Drosophila melanogaster, along with its impact on the gene expression of Notch; additionally, Sertraline, a selective serotonin reuptake inhibitor (SSRI) used to treat mental conditions, was evaluated for its potential to ameliorate MEGF10 myopathy in Drosophila. Using the Climbing and Larval Crawling assay, I studied the locomotor abilities of treated and untreated mutant flies. Drpr deficiency decreased locomotor skills in adult and larval flies. Sertraline had no ameliorating effects on the climbing ability of mutants. However, improvement in crawling behavior by sertraline depended on the genotype of the larvae. Gene expression of the Notch was also assessed using real-time PCR. Notch expression appeared to be reduced in Drpr-/- compared to Notch mutants. My findings suggest that while sertraline holds promise as a therapeutic for MEGF10 myopathy, its efficacy is limited. Future research could focus on its mechanism of action while also exploring newer therapeutic drugs.

Open Access Agreement

On-Campus only

Creative Commons License

Creative Commons License
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