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

Curr Biol. 2020 Apr 6;30(7):1189-1198.e5. doi: 10.1016/j.cub.2020.01.049. Epub 2020 Feb 13.

Abstract

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.

Keywords: Drosophila; axon targeting; glomeruli; neuronal type; olfactory receptor; olfactory receptor neurons; olfactory system; single-cell RNA-seq.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / physiology
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Olfactory Receptor Neurons / physiology*
  • POU Domain Factors / genetics*
  • POU Domain Factors / metabolism
  • Receptors, Odorant / genetics*
  • Receptors, Odorant / metabolism
  • Single-Cell Analysis
  • Smell / physiology
  • Transcriptome*

Substances

  • Drosophila Proteins
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • POU Domain Factors
  • Receptors, Odorant
  • fkh protein, Drosophila
  • unpg protein, Drosophila
  • acj6 protein, Drosophila