The neurons of the vertebrate nervous system are produced by a wave of neurogenesis during development, and in general, mature neurons that are destroyed will not be replaced. The only region of the mature nervous system in which degenerated neurons are replaced is the olfactory sensory epithelium. These neurons are produced originally by a population of neurogenic basal cells. But, when the epithelium reaches its mature configuration, the basal cells become mostly quiescent. When the mature neurons are destroyed, either by natural processes or by experimental manipulation, the basal cells become mitotically active, undergo neuro- genesis and replace the missing neurons. The mechanisms that prevent the basal cells of the quiescent epithelium from producing neurons, and the mechanisms that induce the quiescent basal cells to become neurogenetic basal cells in response to the loss of mature neurons are not known. It is likely that the inhibition and induction of olfactory neurogenesis are mediated by peptide signaling molecules because peptides have been shown to mediate similar events in other tissues. The experiments proposed herein will use biochemical methods to identify peptide signalling molecules that regulate olfactory neurogenesis by searching for proteins that are synthesized preferentially by mature olfactory neurons, by degenerating olfactory neurons and by basal cells that are involved in neurogenesis. These proteins will be sought by administering radiolabeled amino acids to olfactory epithelia in which most of the neurons are involved in one of these events. The neuronal population will be synchronized by destroying the neurons with Zinc so that they are replaced with a population of neurogenetic basal cells. This innovative approach represents the first direct search for factors that regulate olfactory neurogenesis. These proteins may help to elucidate why neurogenesis continues in the mature olfactory epithelium and why it does occur in other sensory systems, and may ultimately provide a means to prevent or cure degenerative disorders of sensory systems.
| Richard, Céline; Doherty, Joni K; Fayad, Jose N et al. (2015) Identification of target proteins involved in cochlear otosclerosis. Otol Neurotol 36:923-31 |
