Exocytosis coordinates epithelial cell-turnover inDrosophilaribosomal protein mutants

Abstract

AbstractRobust tissue growth is orchestrated by the precise coordination of cell death and cell proliferation. Our previous study found that in the developing wing pouches ofDrosophila Minute/+ animals, both cell death and compensatory cell proliferation are dramatically increased, which contributes to robust growth of mutant tissue. The induction of this cell-turnover depends on activation of JNK signaling, although the mechanism by which JNK activation causes cell-turnover remained unclear. Here, we found that JNK-mediated elevation of exocytosis in dying cells is crucial for inducing cell-turnover inM/+wing morphogenesis. Mechanistically, elevated JNK signaling in dying cells upregulates exocytosis-related genes and Wingless (Wg), leading to enhanced Wg secretion. Our data also suggested that secreted Wg from dying cells enhances Wg signaling activity in neighboring living cells via their Frizzled-2 (Fz2) receptors. This interaction between dying cells and their neighboring living cells is pivotal in determining cell fate, dictating which cells will undergo apoptosis and which cells will proliferate. Our findings provide mechanistic insights into the complex interplay between cell death and proliferation, governed by exocytosis and Wg signaling, in coordinating robust tissue growth.