ArticlePLoS biology2026
Beat- and Side-family cell-surface molecules are expressed combinatorially in the partner neurons of the olfactory circuit in Drosophila.
Article in PLoS biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Over the past decades, many molecular players have been uncovered to control distinct steps of olfactory circuit assembly in Drosophila. Among these, multi-member gene families encoding cell-surface proteins are of interest as they can act as neuron-specific recognition tags in combinations and contribute to circuit assembly in complex brains. Recently, a multi-protein interactome has been described between Beat and Side families of IgSF proteins. Here, we use newly generated gene trap transgenic driver lines to probe the spatial expression pattern of beat/side genes in olfactory receptor neurons (ORNs) and their synaptic target projection neurons (PNs). Our results revealed that each ORN/PN class expresses a specific combination of beat/side genes, hierarchically regulated by lineage-specific genetic programs. To explore whether the class-specific expression of beats/sides defines ORN-PN matching specificity, we perturbed presynaptic beat-IIa and postsynaptic side-IV in two ORN-PN partners. However, disruption of Beat-IIa-Side-IV interaction did not produce any significant mistargeting in these two examined glomeruli. Our expression mapping revealed that the Beat/Side interactome between ORNs and PNs appears to be error-tolerant, supporting the robust trans-synaptic recognition. Though without affecting general glomerular targeting, knockdown of side in ORNs leads to the reduction of synaptic development. Interestingly, we found conserved expression patterns of beat/side orthologs across ORNs in ants and mosquitoes, indicating the shared regulatory strategies specifying the expression of these duplicated paralogs in insect evolution. This also implies the biological significance of beats/sides in ORN circuit development or function, which is preserved under selective pressure across divergent insect lineages. Overall, this comprehensive analysis of expression patterns lays a foundation for in-depth functional investigations into how Beat/Side combinatorial expression contributes to the olfactory circuit assembly.
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