RNAi targeted to the Mary Shelley gene in Drosophila melanogaster resulting in phenotypic alterations that can be used to model human tumor development.

Dykema, Paige, Joseph Samona, Chelsea Watkins, and Jacob Kagey

We are using RNAi to study the effects of the loss of expression of the Drosophila melanogaster gene CG6191, which we have named Mary Shelley (MS).  MS is the homolog of the human gene CABLES-1, which has frequently been shown to be down regulated in ovarian and other types of cancer. Using the UAS/Gal4 system from yeast, we can target the RNAi expression to different locations within the fly.  Driving RNAi throughout the entire body using the tubulin driver, we have noted temperature dependent phenotypic changes including the reduction of viability.  The engrailed driver targets the RNAi in the posterior compartment of the wing and resulted in temperature dependent alterations in the size and architecture of the wing. Utilizing molecular staining on engrailed RNAi larval wing discs, we have demonstrated that a portion of this change is due to cells dying, via apoptosis, within the wing compartment potentially driven by a deregulation in the wingless pathway.  Understanding the molecular changes that accompany these phenotypes could be helpful in identifying pathways altered in human cancers that have CABLES-1 down regulation.