title: Debra-mediated Ci degradation controls tissue homeostasis in Drosophila adult midgut.
abstract: Adult 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.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Zhouhua
authors: Z
authors: Li
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Yueqin
authors: Y
authors: Guo
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Lili
authors: L
authors: Han
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Yan
authors: Y
authors: Zhang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Lai
authors: L
authors: Shi
authors: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors: Xudong
authors: X
authors: Huang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China ; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Xinhua
authors: X
authors: Lin
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D053823:Hedgehog Proteins / Q000378:metabolism*; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C569735:dbr protein, Drosophila; C467520:esg protein, Drosophila; C100664:smo protein, Drosophila