Investigation of the genetic interactions between the Hippo signaling pathway and Drosophila C-terminal Src kinase (dCsk). Hailey J. Kwon^1,2, Indrayani Waghmare¹, Shilpi Verghese¹, Madhuri Kango-Singh^1,3,4. 1) Department of Biology, University of Dayton, Dayton, OH; 2) University of Dayton Honors Program, Dayton OH; 3) Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton OH; 4) PreMedical Programs, University of Dayton, Dayton OH.

   The Hippo signaling pathway is involved in regulating tissue size and diseases such as cancer. Hippo signaling coordinates a timely transition from cell proliferation to cellular quiescence, and ensures proper cellular differentiation. Aberrant Hippo pathway function (due to mutations or amplification of genes, epigenetic silencing, and oncogenic transformation) is often detected in human cancers and correlates with poor prognosis. The Drosophila C-terminal Src kinase (dCsk) is a genetic modifier of warts (wts), a tumor-suppressor gene in the Hippo pathway, and interacts with the Src oncogene. Reduction in Csk expression and the consequent activation of Src are frequently seen in hepatocellular and colorectal tumors. Previous studies have shown that dCsk regulates cell proliferation and tissue size during development. Given the similarity in the loss of function phenotype of dCsk and wts, we investigated the genetic interactions of dCsk with the Hippo pathway. We hypothesized that dCsk regulates growth via the Hippo pathway. To determine whether dCsk requires Hippo signaling to carry out its growth regulatory functions, two approaches were used. First, we tested if dCsk regulates the expression of transcriptional targets of Hippo signaling, e.g., ex-lacZ, fj-lacZ, dronc1.7kb-lacZ, and diap1-4.3GFP. Second, we tested genetic interactions between dCsk and components of the Hippo pathway in order to determine the hierarchy of gene action. Here we present our progress on establishing the genetic links between dCsk and the Hippo signaling pathway.