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.
Highlights
The digestive tract is uniquely challenged by its high degree of exposure to the external environment
Upon oral infection by entomopathogenic bacteria like Erwinia carotovora ssp. carotovora 15 (Ecc15) or Pseudomonas entomophila (Pe), Unpaired 3 (Upd3) acts as a signal to trigger antibacterial and Transcriptional regulation of upd3 in the Drosophila midgut reparative host responses [17,23]
We characterized this response through Reverse transcription (RT)-qPCR measurements of midgut upd3 expression, taken over the course of a week following ingestion of Ecc15 or Pe
Summary
The digestive tract is uniquely challenged by its high degree of exposure to the external environment. Digestive tissue is constantly exposed to a high density of microbes, including benign microbiota and invasive pathogens [1]. The gut epithelium performs a multifaceted role in maintaining the barrier between the host and its environment through immune responses and the maintenance of a continuous cellular monolayer [2], while digesting and absorbing nutrients. Preservation of epithelial integrity in the GI tract requires continual tissue turnover by coordinated shedding of epithelial cells along with division and differentiation of intestinal stem cells (ISCs) [1,3]. Cytokines, which are central to gut homeostasis, are produced by epithelial and immune cells to properly orchestrate immune and repair responses [2,3]. The control of cytokine signaling in the digestive tract is complex, and characterizing the regulators of cytokine expression is a critical step towards fully understanding the mechanisms underlying intestinal homeostasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
