Odorant receptors can mediate axonal identity and gene choice via cAMP-independent mechanisms

Open Biol. 2016 Jul;6(7):160018. doi: 10.1098/rsob.160018.


Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested to principally rely on G-protein signalling. Here, we report that for a subset of OSNs, deleting G proteins or altering their levels of signalling does not affect axonal identity. Signalling-deficient ORs or surrogate receptors that are unable to couple to Gs/Golf still provide axons with distinct identities and the anterior-posterior targeting of axons does not correlate with the levels of cAMP produced by genetic modifications. In addition, we refine the models of negative feedback by showing that ectopic ORs can be robustly expressed without suppressing endogenous gene choice. In conclusion, our results uncover a new feature of ORs, showing that they can instruct axonal identity and regulate olfactory map formation independent of canonical G-protein signalling and cAMP production.

Keywords: GPCR; axon guidance; gene choice; neuronal wiring; olfaction; olfactory receptor.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Feedback, Physiological
  • Female
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation
  • Male
  • Mice
  • Olfactory Receptor Neurons / metabolism*
  • Receptors, Odorant / genetics*
  • Receptors, Odorant / metabolism
  • Signal Transduction


  • Receptors, Odorant
  • Cyclic AMP
  • GTP-Binding Proteins