title: βν integrin inhibits chronic and high level activation of JNK to repress senescence phenotypes in Drosophila adult midgut.
abstract: Proper control of adult stem cells including their proliferation and differentiation is crucial in maintaining homeostasis of well-organized tissues/organs throughout an organism's life. The Drosophila adult midgut has intestinal stem cells (ISCs), which have been exploited as a simple model system to investigate mechanisms controlling adult tissue homeostasis. Here, we found that a viable mutant of βν integrin (βint-ν), encoding one of two Drosophila integrin β subunits, showed a short midgut and abnormal multilayered epithelia accompanied by an increase in ISC proliferation and misdifferentiation defects. The increase in ISC proliferation and misdifferentiation was due to frequent ISC duplication expanding a pool of ISCs, which was caused by depression of the Notch signalling, and up-regulation of unpaired (upd), a gene encoding an extracellular ligand in the JAK/STAT signalling pathway. In addition, we observed that abnormally high accumulation of filamentous actin (F-actin) was caused in the βint-ν mutant enterocytes. Furthermore, the defects were rescued by suppressing c-Jun N-terminal kinase (JNK) signalling, which was up-regulated in a manner correlated with the defect levels in the above-mentioned βint-ν mutant phenotype. These symptoms observed in young βint-ν mutant midgut were very similar to those in the aged midgut in wild type. Our results suggested that βint-ν has a novel function for the Drosophila adult midgut homeostasis under normal conditions and provided a new insight into possible age-related diseases caused by latent abnormality of an integrin function.
authors.affiliation: Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, Japan ; Graduate Course in Life Science, Graduate School of Science, Gakushuin University, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, Japan.
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, Japan ; Graduate Course in Life Science, Graduate School of Science, Gakushuin University, Tokyo, Japan ; Institute for Biomolecular Science, Gakushuin University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Adachi-Yamada
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016922:Cellular Senescence; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D039641:Integrin beta Chains; C084344:integrin beta5; D048031:JNK Mitogen-Activated Protein Kinases