(A) The scheme of damage induction and recovery. (B) (B–E’) Sox21a (red) expression in the midgut of flies fed with sucrose-soaked diet (B, B’) and DSS-soaked diet (C, C’) as well as the flies of 2 day recovery after DSS feeding (D, D’, E, E’). Compared with sucrose-treated control gut (B, B’), DSS treatment showed rapid decline of Sox21a expression in EBs (C, C’). During the recovery phase, Sox21a was dramatically upregulated in EBs (D, D’) and differentiating ECs (E, E’). (F–H”) Spi-lacZ (red) expression in the midgut of flies treated with sucrose (F–F”) or DSS (G–G”) as well as the flies at the recovery phase after DSS treatment (H–H”). Compared with sucrose-treated midgut, in which Spi-lacZ expression was undetectable (F–F”), DSS treatment induced Spi-lacZ expression (G–G”). Spi-lacZ expression was shut down again at the recovery phase (H–H”). (I) Fluorescence intensity of Sox21a expression in EBs relative to background in the midgut of flies fed with sucrose, DSS and flies at the recovery phase after DSS treatment. Sox21a expression in EB was virtually reduced to background levels in DSS-induced damage phase, and then massively upregulated during the recovery phase (REC). Error bars represent s.e.m. n is as indicated. **** denotes student’s t test p<0.0001 (J) Quantification of pH3+ cells in midguts of indicated genotypes. EB- specific depletion of Spi could partially reduce DSS- induced mitosis, while EB-specific transgene expression of Sox21a could strongly inhibit DSS- induced mitosis. Error bars represent s.e.m. n is as indicated. * denotes student’s t test p<0.05. ***p<0.001. Scale bars: 20 μm.