Fig. 7

Model. a Model for the dynamic control of ISC activity by AWD-facilitated endocytic regulation of Tkv/MAD signaling during the regenerative response. Under homeostatic conditions, Highwire and proteasomes maintain high turn-over of Tkv protein, leading to its absence in ISCs. During the early induction phase after infection, Dpp ligands first bind to constantly expressed Sax, promoting ISC proliferation through Smox signaling. Meanwhile, activated JNK stabilizes Tkv on ISC membrane, potentially by inhibiting proteasomal activity, while upregulating AWD expression. During the late recovery phase, stabilization of Tkv protein followed by AWD-facilitated internalization to early endosomes switches on MAD signaling, allowing a return to ISC quiescence. b Timeline of ISC proliferation and relative expression of Tkv/Sax/Highwire/Awd during one regeneration episode