Debra-Mediated Ci Degradation Controls Tissue Homeostasis in Drosophila Adult Midgut

•Dbr regulates ISC proliferation and midgut homeostasis in Drosophila adult midgut•Dbr controls ISC proliferation through Ci•Elevated Hh signaling induces ISC proliferation•Cytoprotective JNK signaling acts downstream of Hh signaling in ISC proliferation

SummaryAdult tissue homeostasis is maintained by resident stem cells and their progeny. However, the underlying mechanisms that control tissue homeostasis are not fully understood. Here, we demonstrate that Debra-mediated Ci degradation is important for intestinal stem cell (ISC) proliferation in Drosophila adult midgut. Debra inhibition leads to increased ISC activity and tissue homeostasis loss, phenocopying defects observed in aging flies. These defects can be suppressed by depleting Ci, suggesting that increased Hedgehog (Hh) signaling contributes to ISC proliferation and tissue homeostasis loss. Consistently, Hh signaling activation causes the same defects, whereas depletion of Hh signaling suppresses these defects. Furthermore, the Hh ligand from multiple sources is involved in ISC proliferation and tissue homeostasis. Finally, we show that the JNK pathway acts downstream of Hh signaling to regulate ISC proliferation. Together, our results provide insights into the mechanisms of stem cell proliferation and tissue homeostasis control.

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