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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.

Original publication

DOI

10.1371/journal.pgen.1007091

Type

Journal article

Journal

PLoS Genet

Publication Date

11/2017

Volume

13

Keywords

Animals, Bacterial Infections, Cell Proliferation, Drosophila, Drosophila Proteins, Enterocytes, Female, Gene Expression Regulation, Gene Regulatory Networks, Intestines, Intracellular Signaling Peptides and Proteins, MAP Kinase Signaling System, Male, Pectobacterium carotovorum, Protein-Serine-Threonine Kinases, Pseudomonas, Signal Transduction, Stem Cells, Transcription Factors, Transforming Growth Factor beta