View Program - 63rd Annual Drosophila Research Conference

Drosophila share developmental pathways with humans and other organisms, and many of these pathways are disrupted in human tumorigenesis. We are studying the developmental expression patterns and knock-down phenotypes of the Drosophila gene CG6191, which we have named, Mary Shelley (MS). The human homolog of MS is Cables-1 and has been shown to be frequently downregulated in a number of human cancers, such as ovarian and endometrial. Using the MiMIC system, we find that MS expresses in a distinct band along the dorsal/ventral boundary compartment of the wing disc during larval development. The expression of MS is similar to the well-established expression pattern of the Notch and Wingless cell signaling pathway in the wing. To understand the developmental role that MS is playing in wing development, we utilized RNAi knockdown in the posterior compartment. We find that despite the RNAi confined to the posterior compartment, both the posterior and anterior compartments have a reduction in tissue size. This is due to increased apoptosis at the larval stage both autonomously (posterior) and non-autonomously (anterior). This pattern of non-autonomous apoptosis has previously been shown to be facilitated by the JNK signaling pathway. In MS knockdown cells we see an autonomous increase in the expression of the JNK ligand Eiger and a non-autonomous increase in Puckered, suggesting that the non-autonomous apoptosis is driven by aberrant JNK signaling. Currently we are utilizing a dominant-negative Basket allele to determine if the non-autonomous apoptosis observed is dependent upon JNK signaling. Understanding the downstream consequences of MS knockdown will help to better elucidate the developmental role of MS in Drosophila development.

Knockdown of CG6191 (Mary Shelley) results in compensatroy apoptosis in the imaginal wing disc mediated through JNK signaling