Conserved Role of EGFR Signaling in Apoptotic Cell Recognition and Processing Across Different Phagocytes

Efferocytosis is an essential process that clears dying cells from tissues and prevents inflammation. However, the mechanisms by which apoptotic cells recruit and activate phagocytes remain poorly understood. Here, we show that EGFR signaling is both necessary and sufficient for efficient efferocytosis in two diverse phagocytes: the gonadal sheath cells of C. elegans and the zebrafish microglia. In C. elegans, loss of LET 23 EGFR or its downstream effector MPK 1 ERK in the sheath cells impairs the recognition and degradation of apoptotic germ cells. Germ cells undergoing apoptosis secrete the EGF ligand LIN 3, which promotes their recognition and engulfment. Overexpression of EGF in non apoptotic germ cells is sufficient to trigger their engulfment, indicating that EGF can function as an engulfment signal independently of apoptotic cell death. In zebrafish larvae, pharmacological inhibition of EGFR signaling reduces microglial motility, recognition of apoptotic neurons, and corpse clearance in the optic tectum. An ectopic source of EGF serves as an attractive cue that promotes microglial recruitment. Our findings suggest that EGFR signaling controls an evolutionarily conserved efferocytosis module that coordinates the recognition and processing of apoptotic corpses across different phagocytes. Full-text embargoed until: 2026-10-06

Author dc:creator

• Comi, Laura Filomena

• 610 Medicine & health
• 570 Life sciences; biology

Statement dc:rights

• info:eu-repo/semantics/closedAccess

Language dc:language

eng