Genetic analysis of Yorkie-driven overgrowth: depletion of transcriptional targets Open Access

Kim, Alice Jin (2015)

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The Hippo pathway is a conserved signaling pathway for organ growth and development. Current understanding of the Hippo pathway centers on a core of proteins, including a kinase cascade of the Hippo and Warts kinases that transduce extracellular signals from the cell membrane to the nucleus to modulate gene transcription. Studies have revealed that mutations in genes encoding key Hippo components can lead to uncontrolled cell proliferation in humans and flies, making the Hippo pathway a prime suspect in many types of tumorigenesis. The Hippo pathway has been found to be deregulated in human cancers, such liver, colorectal, lung, and ovarian cancer, primarily in two nuclear components YAP1 and TAZ, which are the human homologs of Yorkie (Yki). Studying the deregulation of Yki in D. melanogaster may thus bring insight into the deregulation of the Yki homologs YAP1 and TAZ in human cancers. In the work described herein, two key gaps in our knowledge involving the deregulation of Yki in the Hippo pathway will be investigated: (1) the extent to which Yki interacts functionally with the Taiman (Tai) protein to affect gene expression, and (2) the identity of the full set of genes that are transcriptionally induced by Yki and Tai. Tai had been found to not be absolutely required for overgrowth in ex mutant wing cells, and CG83212 transcript had been found to be a key transcript of Yki:Tai that may contribute to Yki-driven overgrowth.

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List of Figures

I. Background. 1

II. Experimental Approaches. 4

III. Preliminary Data. 5

IV. Methods. 6

V. Results. 9

VI. Discussion. 13

VII. References. 16

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