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

Robust tissue growth is orchestrated by the precise coordination of cell death and cell proliferation. In the developing wing pouches of <i>Drosophila Minute</i>/+ 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 <i>M/+</i> 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 <i>Drosophila Minute/+</i> wing morphogenesis.

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Publication Details

Journal
iScience
Published
2025-05-05
DOI
https://doi.org/10.1016/j.isci.2025.112587
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Shizue Ohsawa, Nanami Akai, Tatsushi Igaki, Yoshimasa Yagi
iScience
CRISPR and Genetic Engineering
article

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

Shizue Ohsawa, Nanami Akai, Tatsushi Igaki, Yoshimasa Yagi
article en

Abstract

Robust tissue growth is orchestrated by the precise coordination of cell death and cell proliferation. In the developing wing pouches of <i>Drosophila Minute</i>/+ 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 <i>M/+</i> 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 <i>Drosophila Minute/+</i> wing morphogenesis.

iScienceVol. 28(6)
Kyoto University (JP), Nagoya University (JP)
Takeda Science Foundation, Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science, Japan Science and Technology Agency
Zero hunger
Openalex Percentile: Top 91%
CRISPR and Genetic Engineering
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