Fig. 4.

JAK/STAT signaling during regeneration of the Drosophila wing disc. After genetic or mechanical ablation, ROS are produced by damaged cells (red), leading to autonomous JNK activation, which ensures commitment to apoptosis through a positive-feedback loop between JNK and Hid or Rpr. ROS produced by damaged cells also non-autonomously activate JNK and p38 in neighboring healthy, surviving cells (blue). JNK activation in dying cells may be propagated non-autonomously to surviving cells by Egr/TNFα. In the surviving cells, JNK signaling can induce proliferation. Additionally, JNK and p38 independently induce the expression of Upd, which subsequently activates Stat92E (pStat92E) in an autocrine and paracrine manner. pStat92E then increases the proliferation of surviving cells and inhibits apoptosis. pStat92E may also upregulate Dilp8 (dashed line), thereby promoting developmental delay. pStat92E in surviving cells is required for their plasticity and the ability to be ‘reprogrammed’ to other wing lineages. CtBP strongly inhibits JNK signaling and weakly inhibits JAK/STAT signaling cell-autonomously. Finally, pStat92E together with JNK activity downstream of Egr can trigger the formation of an ectopic wing blade (‘mis-specification’).