RRC ID 49572
著者 Houtz P, Bonfini A, Liu X, Revah J, Guillou A, Poidevin M, Hens K, Huang HY, Deplancke B, Tsai YC, Buchon N.
タイトル Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.
ジャーナル PLoS Genet.
Abstract Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.
巻・号 13(11)
ページ e1007091
公開日 2017-11-7
DOI 10.1371/journal.pgen.1007091
PMID 29108021
PMC PMC5690694
MeSH Animals Bacterial Infections / genetics Bacterial Infections / metabolism* Cell Proliferation Drosophila / genetics* Drosophila / microbiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism Enterocytes / metabolism Female Gene Expression Regulation Gene Regulatory Networks Intestines / cytology Intestines / microbiology Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism MAP Kinase Signaling System Male Pectobacterium carotovorum / metabolism Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Pseudomonas / metabolism Signal Transduction* Stem Cells / microbiology Transcription Factors / genetics Transcription Factors / metabolism Transforming Growth Factor beta / genetics Transforming Growth Factor beta / metabolism
ショウジョウバエ 7873R-2 7873R-3 7524R-1