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dc.contributor.advisorWANG, JIANen_US
dc.contributor.authorDu, Lijuanen_US
dc.date.accessioned2015-02-07T06:31:31Z
dc.date.available2015-02-07T06:31:31Z
dc.date.issued2014en_US
dc.identifierdoi:10.13016/M2JK6R
dc.identifier.urihttp://hdl.handle.net/1903/16257
dc.description.abstract<italic>Drosophila</italic> mushroom bodies, centers of olfactory learning and memory, are generated by four neuroblasts in each brain hemisphere. Through a forward genetic screen, I found that mutations in the Janus Kinase (JAK) / Signal Transducer and Activator of Transcription (STAT) pathway genes <italic>domeless</italic> (<italic>dome</italic>) and <italic>hopscotch</italic> (<italic>hop</italic>) cause precocious disappearance of mushroom body neuroblasts. Further evidence indicates that JAK/STAT signaling prevents neuroblast termination and promotes neuroblast division in <italic>Drosophila</italic> mushroom bodies. Remarkably, ectopic expression of <italic>yorkie</italic> (<italic>yki</italic>), the downstream effector of the Hippo signaling pathway, efficiently rescues <italic>dome</italic> mutant phenotypes, and overexpression of Yki target-genes <italic>CycE</italic> or/and <italic>Diap1</italic> partially rescues the &#947;-only phenotype that results from lack of JAK/STAT signaling. Further studies indicate that loss of <italic>yki</italic> function causes a similar but less severe phenotype in mushroom bodies, and this phenotype could be rescued by dominant activation of JAK/STAT. I conclude that both JAK/STAT and Yki activities are required for mushroom body neurogenesis, and higher levels of one can compensate for lack of the other. I also found that Stat92E directly controls <italic>CycE</italic> expression in mushroom body neuroblasts via a consensus STAT-binding site. Furthermore, mushroom body neuroblast clones with no <italic>CycE</italic> expression or an excess of <italic>CycE</italic> expression phenocopy mushroom bodies with decreased or increased JAK/STAT signaling activities, respectively. Together these results suggest that <italic>CycE</italic> is transcriptionally regulated by STAT92E and is required for mediating cell proliferation. Moreover, I showed that Stat92E and Yki regulate the transcription of <italic>CycE</italic> by interacting with two independent enhancers. It is known that the transcription factor <italic>E2f1</italic> is induced by Yki, and my transgenic analysis suggested that two STAT-binding sites are required for <italic>E2f1</italic> expression in <italic>Drosophila</italic> brain and wing disc. Therefore, <italic>E2f1</italic> is another shared target of Stat92E and Yki. Together with the findings of others that <italic>Diap1</italic> is a direct target of STAT92E and Yki, I propose that JAK/STAT and Hippo signaling pathways are integrated to control development of <italic>Drosophila</italic> by independently regulating the transcription of common target genes, such as <italic>CycE</italic> and <italic>E2f1</italic> to control cell proliferation, and <italic>Diap1</italic> to control cell survival.en_US
dc.language.isoenen_US
dc.titleJAK/STAT AND HIPPO SIGNALING PATHWAYS INDEPENDENTLY REGULATE THE SAME TARGET GENES TO CONTROL CELL PROLIFERATIONen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentMolecular and Cell Biologyen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pqcontrolledDevelopmental biologyen_US
dc.subject.pquncontrolledCELL PROLIFERATIONen_US
dc.subject.pquncontrolledCYCLIN Een_US
dc.subject.pquncontrolledHIPPO PATHWAYen_US
dc.subject.pquncontrolledJAK/STAT PATHWAYen_US


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