Silencing of drpr leads to muscle and brain degeneration in adult Drosophila

Abstract

Mutations in MEGF10 underlie a novel autosomal recessive congenital muscle disease in humans. To explore the role of MEGF10 in muscle, we studied its Drosophila homolog, drpr, in muscle function and anatomy. We show that adult drpr null flies display shortened lifespan and locomotor defects associated with abnormal positioning of the legs. RNAi‐mediated down‐regulation of drpr expression in the entire organism, or targeted to muscle cell progenitors, results in an age‐dependent decrease in motor activity. Histological analysis of drpr mutants reveals abnormalities in both the brain and muscle, in contrast to the human phenotype which only affects skeletal muscle. The absence of functional redundancy for drpr in Drosophila may help elucidate whether paralogs of MEGF10 in humans (e.g. MEGF11) contribute to maintaining wild‐type function in the human brain. Homologous mammalian proteins may be introduced in the fly mutant background to study the in vivo function of the wild‐type protein and the effects of mutations. Our Drosophila models will help delineate the physiologic relevance of the MEGF10/drpr pathway in muscle function and disease. This study was funded by the Muscular Dystrophy Association and a Boston Children's Hospital Pilot Grant.