Repulsive interactions instruct synaptic partner matching in an olfactory circuit

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Cell-surface proteins (CSPs) mediate attractive interactions crucial for synaptic partner matching.
• The role of repulsive CSPs in guiding precise neural connections remains less understood.

Purpose of the Study:

• To investigate the role of repulsive CSPs in synaptic partner matching within the developing Drosophila olfactory system.
• To identify specific CSPs involved in mediating repulsive interactions between olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites.

Main Methods:

• Utilized a genetic screen informed by single-cell transcriptomics data.
• Investigated three identified CSP pairs: Toll2-Ptp10D, Fili-Kek1, and Hbs/Sns-Kirre.
• Analyzed gene expression patterns and loss-of-function/overexpression phenotypes.

Main Results:

• Identified three CSP pairs mediating repulsive interactions between non-cognate ORN and PN partners.
• Demonstrated inverse expression patterns of these CSP pairs in target neurons.
• Showed that loss or overexpression of CSPs in one neuron type affects synaptic matching with its partner neuron.

Conclusions:

• Multiple repulsive CSP pairs actively prevent inappropriate connections during neural development.
• These repulsive interactions are essential for ensuring precise synaptic partner matching in the Drosophila olfactory circuit.
• The identified CSPs are differentially expressed in other brain regions, suggesting broader roles in neural wiring.