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

**Authors:** Nanami Akai, Yoshimasa Yagi, Tatsushi Igaki, Shizue Ohsawa

PMC · DOI: 10.1016/j.isci.2025.112587 · iScience · 2025-05-05

## TL;DR

The study reveals how JNK signaling and exocytosis work together to control cell death and growth in fruit fly wing development.

## Contribution

The discovery of a JNK-exocytosis feedback loop that coordinates cell turnover and Wg secretion in Drosophila Minute/+ mutants.

## Key findings

- JNK signaling increases exocytosis and Wg secretion in dying cells during Drosophila wing development.
- Elevated exocytosis promotes caspase activation through a feedback loop involving Dronc.
- The JNK-exocytosis-Wg pathway is universally active downstream of JNK signaling, regardless of genetic background.

## Abstract

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.

•JNK-exocytosis axis coordinates robust tissue growth in Minute/+ wing morphogenesis•JNK signaling upregulates exocytosis-related genes and Wg, leading to Wg secretion•Elevated exocytosis promotes caspase activation via a feedback loop with Dronc

JNK-exocytosis axis coordinates robust tissue growth in Minute/+ wing morphogenesis

JNK signaling upregulates exocytosis-related genes and Wg, leading to Wg secretion

Elevated exocytosis promotes caspase activation via a feedback loop with Dronc

Cell biology; Functional aspects of cell biology; Developmental biology

## Linked entities

- **Genes:** Minute (minute imprinted gene in the Igf2 region) [NCBI Gene 107894], MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599], wg (Wnt family member 1 wingless) [NCBI Gene 692745], WG (Wegener granulomatosis) [NCBI Gene 474168], Dronc (Death regulator Nedd2-like caspase) [NCBI Gene 39173]
- **Species:** Drosophila (taxon 7215)

## Full-text entities

- **Genes:** Dcp-1 (Death caspase-1) [NCBI Gene 37729] {aka CG5370, DCP1, Dcp1, Dmel\CG5370, cDcp, cDcp-1}, RpS17 (Ribosomal protein S17) [NCBI Gene 39088] {aka BcDNA:RE44119, CG3922, D9, Dmel\CG3922, M, M(3)67}, Dronc (Death regulator Nedd2-like caspase) [NCBI Gene 39173] {aka CG8090, CG8091, Dmel\CG8091, Dronc/Casp9, Nc, Nc\Dronc}, bsk (basket) [NCBI Gene 44801] {aka Basket, CG5680, D-JNK, D-junk, DBSK/JNK, DJNK}
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12159887/full.md

## References

90 references — full list in the complete paper: https://tomesphere.com/paper/PMC12159887/full.md

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Source: https://tomesphere.com/paper/PMC12159887