The regulation of Dronc by Hippo Pathway. Shilpi Verghese¹, Aidan Fenix¹, Madhuri Kango-Singh^1,2,3. 1) Department of Biology, University of Dayton, Dayton, OH; 2) Pre-Medical Programs, University of Dayton, Dayton OH; 3) Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton OH.

   Hippo pathway regulates organ size by maintaining a fine balance between cell death and proliferation by regulating the transcription of several target genes including diap1, myc, ex, bantam miRNA, head involution defective (hid), Drosophila Nedd-2 like caspase (dronc) and cyclin E. Loss of Hippo signaling causes proliferation by increased activity of its transcriptional co-activator Yorkie (Yki); whereas gain of Hippo signaling by hyperactivation of genes like Hippo causes cell death via Jun N-terminal Kinase (JNK) and Caspase mediated cell death pathways. We found that loss of warts (wts) induces dronc transcription suggesting that Dronc is normally activated by Hippo signaling unlike other reported target genes. We will test the mechanism of dronc regulation by Hippo signaling. Mammalian Yorkie homologs (YAP, TAZ) act both as transcriptional co-activators/repressors. YAP regulates apoptosis through p73- a p53 family transcription factor. The p53 family [p73, p63, p53] regulates growth, apoptosis and DNA damage response. Drosophila p53(Dmp53) is the sole p53 family gene in flies, and Dmp53 regulates dronc transcription for the regulation of irradiation-dependent and independent compensatory proliferation. The Hippo pathway may regulate dronc transcription through or independent of Yki to regulate organ size. Using GAL4-UAS and transgenic RNAi approaches, we tested for interaction between Dmp53, Hippo pathway and Dronc to investigate the mechanism by which Hippo pathway controls dronc transcription. Over expression of full length Dmp53 enhances the cell death caused by Hippo over-expression while loss of Dmp53 and hpo (using RNAi) in the wing pouch (using nubGAL4) down-regulates dronc transcription suggesting that Dmp53 acts downstream of Hippo pathway. We present our studies of the interaction between the Hippo pathway and Dmp53 in the regulation of dronc transcription.