Sequential expression of Trks A, B, and C in the regenerating olfactory neuroepithelium

This study examines how the family of neurotrophin receptor tyrosine kinases (Trks) participates in the regeneration and replacement of olfactory neurons within the adult rat olfactory neuroepithelium. mRNA and protein products representing the high-affinity nerve growth factor (NGF) receptor Trk A, its family members Trk B and Trk C, and the low-affinity NGF receptor (INGFR) are all detected within both mature and regenerating olfactory neuroepithelium and within primary cultures of olfactory neurons. Cellular immunoreactivity for Trks A, B, and C and INGFR changes dramatically during the lifetime of an olfactory neuron and is demonstrated by inducing the epithelium into a coordinate rapid cycle of degeneration and regeneration in vivo by removal of the target organ, the olfactory bulb. Trk A-positive neuronal precursor basal cells undergo mitosis to produce Trk B-positive immature neurons that mature under the local influence of the olfactory neuroepithelium and the target-derived influence of the olfactory bulb to become a Trk C-positive mature neuron. Primary cultures of immature olfactory neurons demonstrate neurotrophin-induced phosphorylation of Trks A, B, and C and subsequent activation of the immediate early gene c-Fos, and they change their expression of differentiation stage-specific markers after treatment with individual and combinations of neurotrophins. This is the first population of neurons of a single lineage in which Trks A, B, and C and the INGFR have been demonstrated to be expressed sequentially during neuronal division, commitment, and differentiation and to be fully capable of transducing cellular signals causing phenotypic changes in differentiation state.