Function of JAK/STAT and Hippo signaling pathways on Drosophila mushroom body neuroblast maintenance and cell proliferation. Lijuan Du¹, Jian Wang^1,2. 1) Molecular and Cell Biology Program, University of Maryland, College Park, MD; 2) Entomology Department, University of Maryland, College Park, MD.

   Mushroom bodies are a pair of prominent structures in the brains of all insects and other arthropods, which play important roles in olfactory learning and memory. Therefore, they are analogous to mammalian hippocampus. Through a forward genetic screen, we found that mutations in genes of the Janus Kinase (JAK) / Signal Transducer and Activator of Transcription (STAT) pathway components domeless (dome) and hopscotch (hop) cause precocious disappearance of mushroom body neuroblasts at early 3rd instar larval stage, which results in fewer number of mushroom body neurons. Surprisingly, ectopic expression of Yorkie (Yki), the downstream effector of Hippo signaling pathway, efficiently rescues dome mutant phenotypes. And overexpression of Yki target genes cycE or diap1 partially rescues the -only phenotype of lacking JAK/STAT action. Further studies indicate that loss of Yki function caused the similar -only phenotype in adult mushroom bodies, and this phenotype could be rescued by dominant activation of JAK/STAT. We conclude that both JAK/STAT and Hippo pathways, which are key regulators of cell proliferation and normal growth in flies and mammals, are required for the normal development of mushroom body neurons, and they can complement each other. By examining the STAT-binding sites at cycE promoter region via transgenic studies, our data demonstrates that cycE is a direct target of STAT92E. Knowing that diap1 is a direct target of STAT92E, our studies firstly show that JAK/STAT and Hippo signaling pathways, which have opposite effects on cell proliferation, are integrated to control development of different tissues in Drosophila by regulating common transcriptional targets, such as cycE and diap1.