Odorant receptor proteins in olfactory axons and in cells of the cribriform mesenchyme may contribute to fasciculation and sorting of nerve fibers

Odorant receptors (ORs) have been shown to be present not only in the chemosensory cilia of the olfactory sensory neurons, but also in their axon terminals. This observation has emphasized the notion that the receptor protein may contribute to the precise receptor-specific targeting of olfactory axons in the olfactory bulb. This concept implies a particularly important role for the axonal receptor protein during the onset and early phase of the wiring process during development. In the present study, we have demonstrated, by means of specific antibodies, that, as early as mouse embryonic day E12, the OR protein can be visualized in outgrowing axonal processes of the olfactory epithelium and in cells located in the cribriform mesenchyme. On their trajectory from the olfactory epithelium through the cribriform mesenchyme toward the forebrain, axons with strong OR immunoreactivity have only been seen in the dorsal part of the mesenchyme where they traverse the region of OR-positive cells. Upon visualization by specific antibodies, these cells have been revealed to have long protrusions extending along the surface of nerve fascicles. They are often located at bifurcations where two small axon fascicles merge to form a stronger bundle. Within this region, fascicles coalesce forming a coherent nerve. Moreover, within the now compact nerve bundle, axons visualized by the OR-specific antibody are no longer distributed evenly but are segregated from other axonal populations within the nerve. These findings suggest that OR proteins in the membrane of axonal processes and of cells in the cribriform mesenchyme are involved in crucial processes such as fasciculation and the sorting of outgrowing axons, both of which are fundamental for the initiation and establishment of the precise wiring of the olfactory system during early development.