Homeostatic Epithelial Renewal in the Gut Is Required for Dampening a Fatal Systemic Wound Response in Drosophila
Asuka Takeishi,
Erina Kuranaga,
Ayako Tonoki,
Kazuyo Misaki,
Shigenobu Yonemura,
Hirotaka Kanuka,
Masayuki Miura
Affiliations
Asuka Takeishi
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, 113-0033, Japan
Erina Kuranaga
Laboratory for Histogenetic Dynamics, RIKEN Center for Developmental Biology, Kobe, 650-0047, Japan
Ayako Tonoki
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba, 260-8675, Japan
Kazuyo Misaki
Electron Microscope Laboratory, RIKEN Center for Developmental Biology, Kobe, 650-0047, Japan
Shigenobu Yonemura
Electron Microscope Laboratory, RIKEN Center for Developmental Biology, Kobe, 650-0047, Japan
Hirotaka Kanuka
Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, 105-8461, Japan
Masayuki Miura
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, 113-0033, Japan
Effective defense responses involve the entire organism. To maintain body homeostasis after tissue damage, a systemic wound response is induced in which the response of each tissue is tightly orchestrated to avoid incomplete recovery or an excessive, damaging response. Here, we provide evidence that in the systemic response to wounding, an apoptotic caspase pathway is activated downstream of reactive oxygen species in the midgut enterocytes (ECs), cells distant from the wound site, in Drosophila. We show that a caspase-pathway mutant has defects in homeostatic gut cell renewal and that inhibiting caspase activity in fly ECs results in the production of systemic lethal factors after wounding. Our results indicate that wounding remotely controls caspase activity in ECs, which activates the tissue stem cell regeneration pathway in the gut to dampen the dangerous systemic wound reaction.
