Role of the Pvr signaling Pathway in a Fly Model for Myotonic Dystrophy Type 1

By Maya Takashima, Huda Al-Bana, Grace Holcomb

Faculty Mentor: Professor Ginny Morriss

Myotonic Dystrophy Type 1 (DM1) is a multi-systemic genetic disorder that causes severe muscle weakening and wasting. The phenotype is caused by a CTG repeat expansion in the 3’ untranslated region in the DMPK gene. Studies have shown several different signaling pathways implicated in the DM1 muscle phenotype; however, one pathway that has not been implicated in DM1 is the platelet-derived growth factor receptor beta (PDGFRβ) signaling pathway. PDGFRβ is involved in cell growth, survival, and skeletal muscle hypertrophy. With this involvement, the pathways deregulation could contribute to the muscle wasting seen in DM1. This project uses a fly model to understand the role of the pvr signaling pathway (PDGFRβ fly equivalent) in muscle wasting due to DM1. Through this fly model, it will be determined which downstream pathway is primarily affected during deregulation. The two downstream pathways targeted are PI3K/Akt and Ras/Mek/Erk. Flybase was utilized to determine the downstream gene targets and fly lines needed to start the fly model. After selecting the gene targets, fly lines were picked that were either overexpression of the gene (UAS – upstream activating sequence) or a knockout. Gal4 promoter lines and CTG repeat lines are also needed. Gal4 promoters drive the expression of the desired gene, and the CTG repeat represents the CTG repeat of DM1. With the fly lines chosen, mating schemes were planned to determine what crosses needed to occur to get the desired progeny. The goal was to end up with a progeny with the Gal4 promoter, CTG repeat, and stock line all in the same fly. In the future, using these progeny, different tests will be completed to look at how the overexpression or knockout affects the muscle wasting phenotype.