JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants

Summary: Robust tissue growth is orchestrated by the precise coordination of cell death and cell proliferation. In the developing wing pouches of Drosophila Minute/+ animals, both cell death and compensatory cell proliferation are increased, thereby contributing to robust growth of mutant tissue. He...

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Main Authors: Nanami Akai, Yoshimasa Yagi, Tatsushi Igaki, Shizue Ohsawa
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S258900422500848X
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author Nanami Akai
Yoshimasa Yagi
Tatsushi Igaki
Shizue Ohsawa
author_facet Nanami Akai
Yoshimasa Yagi
Tatsushi Igaki
Shizue Ohsawa
author_sort Nanami Akai
collection DOAJ
description Summary: Robust tissue growth is orchestrated by the precise coordination of cell death and cell proliferation. In the developing wing pouches of Drosophila Minute/+ animals, both cell death and compensatory cell proliferation are increased, thereby contributing to robust growth of mutant tissue. Here, we show that JNK-mediated elevation of exocytosis in dying cells is crucial for triggering cell turnover in M/+ wing morphogenesis. Mechanistically, elevated JNK signaling in dying cells upregulates exocytosis-related genes and Wingless (Wg), leading to enhanced Wg secretion. Notably, increased exocytosis promotes caspase activation via an exocytosis-Dronc amplification loop, sustaining apoptotic signaling while reinforcing Wg secretion through Dronc activation. Furthermore, this exocytosis-mediated Wg secretion and apoptotic feedback loop universally occurs downstream of JNK signaling, regardless of the genetic background. Overall, our findings provide mechanistic insights into robust tissue growth through the orchestration of cell turnover, primarily via JNK-mediated exocytosis during Drosophila Minute/+ wing morphogenesis.
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spelling doaj-art-e64a1f50c8c64c42b442d2fce82646392025-08-20T03:13:00ZengElsevieriScience2589-00422025-06-0128611258710.1016/j.isci.2025.112587JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutantsNanami Akai0Yoshimasa Yagi1Tatsushi Igaki2Shizue Ohsawa3Group of Genetics, Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, JapanGroup of Genetics, Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, JapanLaboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, JapanGroup of Genetics, Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan; Corresponding authorSummary: Robust tissue growth is orchestrated by the precise coordination of cell death and cell proliferation. In the developing wing pouches of Drosophila Minute/+ animals, both cell death and compensatory cell proliferation are increased, thereby contributing to robust growth of mutant tissue. Here, we show that JNK-mediated elevation of exocytosis in dying cells is crucial for triggering cell turnover in M/+ wing morphogenesis. Mechanistically, elevated JNK signaling in dying cells upregulates exocytosis-related genes and Wingless (Wg), leading to enhanced Wg secretion. Notably, increased exocytosis promotes caspase activation via an exocytosis-Dronc amplification loop, sustaining apoptotic signaling while reinforcing Wg secretion through Dronc activation. Furthermore, this exocytosis-mediated Wg secretion and apoptotic feedback loop universally occurs downstream of JNK signaling, regardless of the genetic background. Overall, our findings provide mechanistic insights into robust tissue growth through the orchestration of cell turnover, primarily via JNK-mediated exocytosis during Drosophila Minute/+ wing morphogenesis.http://www.sciencedirect.com/science/article/pii/S258900422500848XCell biologyFunctional aspects of cell biologyDevelopmental biology
spellingShingle Nanami Akai
Yoshimasa Yagi
Tatsushi Igaki
Shizue Ohsawa
JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants
iScience
Cell biology
Functional aspects of cell biology
Developmental biology
title JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants
title_full JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants
title_fullStr JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants
title_full_unstemmed JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants
title_short JNK signaling coordinates epithelial cell turnover through exocytosis in Drosophila ribosomal protein mutants
title_sort jnk signaling coordinates epithelial cell turnover through exocytosis in drosophila ribosomal protein mutants
topic Cell biology
Functional aspects of cell biology
Developmental biology
url http://www.sciencedirect.com/science/article/pii/S258900422500848X
work_keys_str_mv AT nanamiakai jnksignalingcoordinatesepithelialcellturnoverthroughexocytosisindrosophilaribosomalproteinmutants
AT yoshimasayagi jnksignalingcoordinatesepithelialcellturnoverthroughexocytosisindrosophilaribosomalproteinmutants
AT tatsushiigaki jnksignalingcoordinatesepithelialcellturnoverthroughexocytosisindrosophilaribosomalproteinmutants
AT shizueohsawa jnksignalingcoordinatesepithelialcellturnoverthroughexocytosisindrosophilaribosomalproteinmutants