A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting

Cell. 2006 Dec 1;127(5):1057-69. doi: 10.1016/j.cell.2006.10.031.

Abstract

In the mouse, olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) converge their axons to a specific set of glomeruli in the olfactory bulb. To study how OR-instructed axonal fasciculation is controlled, we searched for genes whose expression profiles are correlated with the expressed ORs. Using the transgenic mouse in which the majority of OSNs express a particular OR, we identified such genes coding for the homophilic adhesive molecules Kirrel2/Kirrel3 and repulsive molecules ephrin-A5/EphA5. In the CNGA2 knockout mouse, where the odor-evoked cation influx is disrupted, Kirrel2 and EphA5 were downregulated, while Kirrel3 and ephrin-A5 were upregulated, indicating that these genes are transcribed in an activity-dependent manner. Mosaic analysis demonstrated that gain of function of these genes generates duplicated glomeruli. We propose that a specific set of adhesive/repulsive molecules, whose expression levels are determined by OR molecules, regulate the axonal fasciculation of OSNs during the process of glomerular map formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Cell Adhesion Molecules / metabolism
  • Ephrin-A5 / genetics
  • Ephrin-A5 / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Neurons, Afferent / cytology*
  • Neurons, Afferent / metabolism*
  • Olfactory Bulb / cytology
  • Protein Binding
  • Receptor, EphA5 / metabolism
  • Receptors, Odorant / genetics
  • Receptors, Odorant / metabolism*

Substances

  • Carrier Proteins
  • Cell Adhesion Molecules
  • Ephrin-A5
  • Kirrel3 protein, mouse
  • Membrane Proteins
  • Receptors, Odorant
  • Receptor, EphA5