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Journal of Neuroscience, Vol 16, 1294-1307, Copyright © 1996 by Society for Neuroscience
Sequential expression of Trks A, B, and C in the regenerating olfactory neuroepithelium
AJ Roskams, MA Bethel, KJ Hurt and GV Ronnett
Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
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.
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