βν integrin inhibits chronic and high level activation of JNK to repress senescence phenotypes in Drosophila adult midgut

Takashi Okumura, Koji Takeda, Kiichiro Taniguchi, Takashi Adachi-Yamada

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12 Citations (Scopus)

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.

Original languageEnglish
Article numbere89387
JournalPLoS One
Volume9
Issue number2
DOIs
Publication statusPublished - 2014 Feb 20
Externally publishedYes

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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