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

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.