# Interplay of EGFR, JNK, and ROS signaling in soma-germline communication in the Drosophila testis

## TL;DR

This study explores how signals between cells in the fruit fly testis help maintain tissue balance and prevent cell death.

## Contribution

It reveals a bidirectional feedback mechanism between EGFR, JNK, and ROS signaling in cyst and germline cells.

## Key findings

- EGFR overactivation increases JNK and p38 signaling in cyst cells and ROS in germline cells.
- Reducing JNK or ROS levels restores germ cell survival.
- Rab35 regulates EGFR and Wengen receptor localization on cyst cells.

## Abstract

Cell communication via signaling exchange plays a pivotal role in multicellular development for building up functional tissues and organs. In the Drosophila testis, a pair of somatic cyst cells (CCs) encapsulate the germline that differentiates through close-range EGFR signaling activation. The Dlg/Scrib/Lgl polarity complex and clathrin-mediated endocytosis attenuate EGFR signaling in CCs, and loss of their function leads to EGFR overactivation and death of the neighboring germ cells. Here, we show that EGFR overactivation leads to upregulation of JNK and p38 signaling in CCs and ROS levels in germ cells destined to die. Our data uncover a bidirectional-feedback mechanism between JNK signaling and ROS who regulate each other, while reducing the levels of either JNK or ROS restored germ cell survival. This study provides a framework of how polarity and cellular trafficking regulate the output of multiple signaling responses cell-intrinsically and across cells, to coordinate tissue-specific responses and maintain homeostasis.

•Dlg, Scrib, Lgl, and clathrin-mediated endocytosis regulate EGFR, JNK, and p38 signaling•EGFR overactivation upregulates JNK and p38 signaling in cyst cells and ROS in the germline•EGFR, JNK, & ROS mediate bidirectional feedback between cyst cells & encapsulated germ cells•GTPase Rab35 regulates EGFR and Wengen receptor localization on cyst cells

Dlg, Scrib, Lgl, and clathrin-mediated endocytosis regulate EGFR, JNK, and p38 signaling

EGFR overactivation upregulates JNK and p38 signaling in cyst cells and ROS in the germline

EGFR, JNK, & ROS mediate bidirectional feedback between cyst cells & encapsulated germ cells

GTPase Rab35 regulates EGFR and Wengen receptor localization on cyst cells

This study highlights a bidirectional feedback mechanism that underlies cyst cell-germline reciprocal communication that controls the signaling strength among EGFR, JNK, p38, and ROS within the Drosophila testis cysts.