The Hippo Signaling Pathway in Organ Size Control and Regeneraton

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Title: The Hippo Signaling Pathway in Organ Size Control and Regeneraton
Author: Ren, Fangfang
Abstract: The Hippo (Hpo ) signaling pathway controls cell growth , proliferation and apoptosis in both Drosophila and vertebrates . Our lab has previously demonstrated that Hpo signaling regulates gene expression by inhibiting a transcription complex consisting of the transcriptional coactivator Yorkie (Yki ) and the TEAD /TEF family of transcription factor Scalloped (Sd ) in Drosophila . The inhibition of Yki activity is through modulating its phosphorylation status and subcellular localization by upstream kinase complex . I obtained both genetic and cellular evidence that 14 -3 -3 proteins are involved in this process . I also identified three Serine residues (S111 , S168 and S250 of Yki as essential for restricting Yki activity . I found that 14 -3 -3 regulates Yki subcellular localization mainly through S168 but not the other two sites . The recent identification of intestinal stem cells (ISCs ) has made the Drosophila adult midgut an excellent model to study adult stem cell biology . Multiple signaling pathways have been implicated in the regulation of ISC proliferation , self -renewal and differentiation . I obtained evidence that Hpo signaling plays an essential role in regulating ISC proliferation through both cell -autonomous and non -cell -autonomous mechanisms . Cytokines of the Upd family and multiple EGFR ligands were found to be ectopically induced when Hpo signaling is inactivated in differentiated cells , which in turn activate Jak -Stat and EGFR signaling pathways in ISCs to stimulate their proliferation . I also showed that tissue damaging reagent DSS -induced ISC proliferation is dependent on Yki activity in precursor cells . Although several signaling pathways including Jak -Stat , EGFR and Hpo pathways have been implicated in damage -induced ISC proliferation , the cell intrinsic mechanisms have remained elusive . I found that the Drosophila homolog of Myc oncogene (dMyc ) , which encodes a transcription regulator that affects cellular growth and cell cycle progression , functions downstream of Hpo , Jak -Stat and EGFR pathways to mediate their effects on ISC proliferation . dMyc is also essential for adult midgut homeostasis as well as regeneration after exposure to damage reagents . I also demonstrated that the regulation of dMyc levels by Hipo , Jak -Stat and EGFR pathways is at the level of transcription . [Keywords : Drosphila , hippo , Yki , instestine stem cell , regeneration]
URI: http : / /hdl .handle .net /2152 .5 /1005
Date: 2012-07-17

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The Hippo Signaling Pathway in Organ Size Control and Regeneraton. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /1005 .

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