EGFR signaling modulates synaptic connectivity via Gurken

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Signaling

Background:

• Establishing functional neuronal circuits relies on precise synaptic target selection.
• The molecular mechanisms governing how neurons choose their targets are not fully understood.

Purpose of the Study:

• To investigate the role of Epidermal Growth Factor Receptor (EGFR) signaling in the target selection of octopaminergic Type II neurons in the Drosophila neuromuscular system.
• To identify the specific ligand and mechanism by which EGFR signaling regulates this process.

Main Methods:

• Utilized Drosophila mutants in happyhour, a key regulator of EGFR signaling.
• Analyzed the formation of neuromuscular junctions in these mutants.
• Investigated the necessity and sufficiency of EGFR signaling in target selection.
• Identified the source and function of the EGFR ligand Gurken.

Main Results:

• Mutants lacking proper EGFR signaling exhibited ectopic Type II neuromuscular junctions, indicating aberrant target selection.
• EGFR signaling was found to be both necessary and sufficient to inhibit inappropriate synaptic targeting by Type II neurons.
• Gurken, a ligand for EGFR, was identified as a repulsive cue secreted by the muscle (postsynaptic target).

Conclusions:

• EGFR signaling, mediated by muscle-derived Gurken, acts as a repulsive cue to prevent octopaminergic Type II neurons from forming ectopic synapses.
• This study uncovers a novel pathway for cell-type and branch-specific synaptic repulsion.
• Identified a new role for EGFR signaling in synaptic target selection and an unexpected function for Gurken as a muscle-secreted repulsive ligand.