Epidermal growth factor receptor signaling protects epithelia from morphogenetic instability and tissue damage in Drosophila

Dying cells in the epithelia communicate with neighboring cells to initiate coordinated cell removal to maintain epithelial integrity. Naturally occurring apoptotic cells are mostly extruded basally and engulfed by macrophages. Here, we have investigated the role of Epidermal growth factor (EGF) receptor (EGFR) signaling in the maintenance of epithelial homeostasis. In Drosophila embryos, epithelial tissues undergoing groove formation preferentially enhanced extracellular signal-regulated kinase (ERK) signaling. In EGFR mutant embryos at stage 11, sporadic apical cell extrusion in the head initiates a cascade of apical extrusions of apoptotic and non-apoptotic cells that sweeps the entire ventral body wall. Here, we show that this process is apoptosis dependent, and clustered apoptosis, groove formation, and wounding sensitize EGFR mutant epithelia to initiate massive tissue disintegration. We further show that tissue detachment from the vitelline membrane, which frequently occurs during morphogenetic processes, is a key trigger for the EGFR mutant phenotype. These findings indicate that, in addition to cell survival, EGFR plays a role in maintaining epithelial integrity, which is essential for protecting tissues from transient instability caused by morphogenetic movement and damage.

Automated summary

Dying cells in the epithelia communicate with neighboring cells to initiate coordinated cell removal to maintain epithelial integrity. Epidermal growth factor (EGF) receptor (EGFR) signaling plays an important role in the maintenance of epithelial homeostasis. In Drosophila embryos, the enhanced extracellular signal-regulated kinase (ERK) signaling in epithelial tissues undergoing groove formation. EGFR mutant embryos show sporadic apical cell extrusion in the head, leading to a cascade of apical extrusions throughout the ventral body wall. This process is apoptosis dependent and can cause massive tissue disintegration in EGFR mutant epithelia. Tissue detachment from the vitelline membrane triggers the EGFR mutant phenotype. Therefore, EGFR not only promotes cell survival but also maintains epithelial integrity.