Regulation of epithelium renewal by the JAK/STAT and EGFR pathways. Upon infection, damaged enterocytes release Upd3. This cytokine activates the JAK/STAT pathway in both progenitor cells (ISCs) and in the surrounding visceral muscles (VMs). JAK/STAT activation in VMs participates in the induction of the EGF vein. In addition, two EGFs, Keren and Spitz, are also secreted by the epithelium. The activation of both the JAK/STAT and EGFR pathways in progenitor cells stimulates their proliferation. The JAK/STAT pathway has a unique role in enteroblast differentiation, while the EGFR pathway is required in enterocytes for proper morphogenesis and delamination of damaged enterocytes following infection with Ecc15. Other ligands of the JAK/STAT pathway (Upd1 and Upd2) may also participate in bacteria-induced ISC proliferation.