Single-Cell Transcriptomes Reveal Diverse Regulatory Strategies for Olfactory Receptor Expression and Axon Targeting

The regulatory mechanisms by which neurons coordinate their physiology and connectivity are not well understood. The Drosophila olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. Each ORN type expresses a unique olfactory receptor, or a combination thereof, and sends their axons to a stereotyped glomerulus. Using single-cell RNA sequencing, we identified 33 transcriptomic clusters for ORNs and mapped 20 to their glomerular types, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN types. Each ORN type expresses hundreds of transcription factors. Transcriptome-instructed genetic analyses revealed that (1) one broadly expressed transcription factor (Acj6) only regulates olfactory receptor expression in one ORN type and only wiring specificity in another type, (2) one type-restricted transcription factor (Forkhead) only regulates receptor expression, and (3) another type-restricted transcription factor (Unplugged) regulates both events. Thus, ORNs utilize diverse strategies and complex regulatory networks to coordinate their physiology and connectivity. [Display omitted] •Single-cell RNA-seq analysis of developing Drosophila olfactory receptor neurons•20 of the 33 transcriptomic clusters of ORNs are mapped to glomerular types•Each ORN type expresses hundreds of transcription factors (TFs)•Homeodomain TF Unpg regulates both olfactory receptor expression and axon targeting In this study, Li et al. perform single-cell RNA sequencing of developing olfactory receptor neurons (ORNs) in Drosophila and reveal that ORNs utilize diverse transcriptional strategies to coordinate their olfactory receptor expression and axon targeting.