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

• DOI: 10.1016/j.cub.2020.01.049
• Publication Date: 2020-02-13T15:27:08Z
• Authors: Hongjie Li; Tongchao Li; Felix Horns; Jiefu Li; Qijing Xie; Chuanyun Xu; Bing Wu; Justus M. Kebschull; Colleen N. McLaug...; Sai Saroja Kolluru; Robert C. Jones; David Vacek; Anthony Xie; David J. Luginbuhl; Stephen R. Quake; Liqun Luo
• Keywords: Homeodomain Proteins; 0303 health sciences; Forkhead Transcription Factors; Nerve Tissue Proteins; Receptors, Odorant; Axons; Olfactory Receptor Neurons; Smell; 03 medical and health sciences; Drosophila melanogaster; POU Domain Factors; Animals; Drosophila Proteins; Single-Cell Analysis; Transcriptome

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.