Axon guidance of mouse olfactory sensory neurons by odorant receptors and the beta2 adrenergic receptor

Cell. 2004 Jun 11;117(6):833-46. doi: 10.1016/j.cell.2004.05.013.


Odorant receptors (ORs) provide the core determinant of identity for axons of olfactory sensory neurons (OSNs) to coalesce into glomeruli in the olfactory bulb. Here, using gene targeting in mice, we examine how the OR protein determines axonal identity. An OR::GFP fusion protein is present in axons, consistent with a direct function of ORs in axon guidance. When the OR coding region is deleted, we observe OSNs that coexpress other ORs that function in odorant reception and axonal identity. It remains unclear if such coexpression is normally prevented by negative feedback on OR gene choice. A drastic reduction in OR protein level produces axonal coalescence into novel, remote glomeruli. By contrast, chimeric ORs and ORs with minor mutations perturb axon outgrowth. Strikingly, the beta2 adrenergic receptor can substitute for an OR in glomerular formation when expressed from an OR locus. Thus, ORs have not evolved a unique function in axon guidance.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Cell Communication / genetics
  • Cell Differentiation / genetics
  • Cilia / genetics
  • Cilia / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Gene Targeting
  • Green Fluorescent Proteins
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Luminescent Proteins
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Olfactory Bulb / cytology
  • Olfactory Bulb / growth & development*
  • Olfactory Bulb / metabolism
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / growth & development*
  • Olfactory Receptor Neurons / metabolism
  • Open Reading Frames / genetics
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / physiology*
  • Receptors, Odorant / genetics
  • Receptors, Odorant / physiology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synapses / metabolism*
  • Synapses / ultrastructure


  • Luminescent Proteins
  • Receptors, Adrenergic, beta-2
  • Receptors, Odorant
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins