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      Cultured cells and wing disc size of silkworm can be controlled by the Hippo pathway

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          Abstract

          Hippo signalling represents a cell proliferation and organ-size control pathway. Yorki (Yki), a component of the Hippo pathway, induces the transcription of a number of targets that promote cell proliferation and survival. The functions of Yki have been characterized in Drosophila and mammals, while there are few reports on silkworm, Bombyx mori. In the present study, we found that BmYki3 facilitates cell migration and cell division, and enlarges the cultured cell and wing disc size. Co-immunoprecipitation results indicated that BmYki3 may interact with thymosin, E3 ubiquitin-protein ligase, protein kinase ASK1, dedicator of cytokinesis protein 1, calcium-independent phospholipase A2 and beta-spectrin. RNA-seq results indicated that 4444 genes were upregulated and 10 291 genes were downregulated after BmYki3 was overexpressed in the cultured cells. GO annotation indicated that the up/downregulated genes were enriched in 268/382 GO terms ( p < 0.01); KEGG analysis showed that the up/downregulated genes were enriched in 49/101 pathways. These findings provided novel information to understand the functions of BmYki3 in a cell proliferation and organ-size control pathway.

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          Most cited references22

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          The Ccr4--not complex.

          The Ccr4-Not complex is a unique, essential and conserved multi-subunit complex that acts at the level of many different cellular functions to regulate gene expression. Two enzymatic activities, namely ubiquitination and deadenylation, are provided by different subunits of the complex. However, studies over the last decade have demonstrated a tantalizing multi-functionality of this complex that extends well beyond its identified enzymatic activities. Most of our initial knowledge about the Ccr4-Not complex stemmed from studies in yeast, but an increasing number of reports on this complex in other species are emerging. In this review we will discuss the structure and composition of the complex, and describe the different cellular functions with which the Ccr4-Not complex has been connected in different organisms. Finally, based upon our current state of knowledge, we will propose a model to explain how one complex can provide such multi-functionality. This model suggests that the Ccr4-Not complex might function as a "chaperone platform". Copyright © 2011 Elsevier B.V. All rights reserved.
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            Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways.

            Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for maintaining tissue homeostasis and replenishing lost cells in response to tissue damage. Here we demonstrate that the Hippo (Hpo) signaling pathway, an evolutionarily conserved pathway implicated in organ size control and tumorigenesis, plays an essential role in regulating ISC proliferation. Loss of Hpo signaling in either midgut precursor cells or epithelial cells stimulates ISC proliferation. We provide evidence that loss of Hpo signaling in epithelial cells increases the production of cytokines of the Upd family and multiple EGFR ligands that activate JAK-STAT and EGFR signaling pathways in ISCs to stimulate their proliferation, thus revealing a unique non-cell-autonomous role of Hpo signaling in blocking ISC proliferation. Finally, we show that the Hpo pathway mediator Yorkie (Yki) is also required in precursor cells for injury-induced ISC proliferation in response to tissue-damaging reagent DSS.
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              The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration.

              Intestinal stem cells (ISCs) in the adult Drosophila midgut proliferate to self-renew and to produce differentiating daughter cells that replace those lost as part of normal gut function. Intestinal stress induces the activation of Upd/Jak/Stat signalling, which promotes intestinal regeneration by inducing rapid stem cell proliferation. We have investigated the role of the Hippo (Hpo) pathway in the Drosophila intestine (midgut). Hpo pathway inactivation in either the ISCs or the differentiated enterocytes induces a phenotype similar to that observed under stress situations, including increased stem cell proliferation and expression of Jak/Stat pathway ligands. Hpo pathway targets are induced by stresses such as bacterial infection, suggesting that the Hpo pathway functions as a sensor of cellular stress in the differentiated cells of the midgut. In addition, Yki, the pro-growth transcription factor target of the Hpo pathway, is required in ISCs to drive the proliferative response to stress. Our results suggest that the Hpo pathway is a mediator of the regenerative response in the Drosophila midgut.
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                Author and article information

                Journal
                Open Biol
                Open Biol
                RSOB
                royopenbio
                Open Biology
                The Royal Society
                2046-2441
                July 2018
                4 July 2018
                4 July 2018
                : 8
                : 7
                : 180029
                Affiliations
                [1 ]School of Biology and Basic Medical Science, Agricultural Biotechnology and Ecological Research Institute, Soochow University , Suzhou, 215123, China
                [2 ]National Engineering Laboratory for Modern Silk, Agricultural Biotechnology and Ecological Research Institute, Soochow University , Suzhou, 215123, China
                [3 ]Agricultural Biotechnology Research Institute, Agricultural Biotechnology and Ecological Research Institute, Soochow University , Suzhou, 215123, China
                Author notes
                [†]

                These authors contributed equally to this work.

                Electronic supplementary material is available online at https://dx.doi.org/10.6084/m9.figshare.c.4139789.

                Author information
                http://orcid.org/0000-0001-6545-727X
                Article
                rsob180029
                10.1098/rsob.180029
                6070717
                29973396
                6c7c239d-9e20-42ee-8f5f-b84039c92b77
                © 2018 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 14 February 2018
                : 12 June 2018
                Funding
                Funded by: National Natural Science Foundation of China, http://dx.doi.org/10.13039/501100001809;
                Award ID: 31272500
                Funded by: Doctoral Program of Higher Education;
                Award ID: 20113201130002
                Funded by: National Basic Research Program of China;
                Award ID: 2012CB114600
                Categories
                1001
                129
                Research
                Research Article
                Custom metadata
                July 2018

                Life sciences
                yorki,bombyx mori,cell proliferation,wing disc size,differential gene expression
                Life sciences
                yorki, bombyx mori, cell proliferation, wing disc size, differential gene expression

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