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DIFFERENTIALLY EXPRESSED GENES IN OLFACTORY NEUROGENESIS

$72,750R21FY2000DCNIH

University Of Kentucky, Lexington KY

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Abstract

DESCRIPTION (adapted from applicant's abstract): The goal of this research is to describe molecular changes that occur during early and intermediate steps in the neurogenesis of olfactory receptor neurons of adult mice. The olfactory receptor neurons are one of the few populations of neurons that undergo continuous replacement in adult vertebrates. While a few examples of gene expression changes in the olfactory receptor neuron lineage are known, they represent only a minute fraction of the changes that must occur. Advances in recombinant DNA technology now make it possible to simultaneously identify large numbers of differentially expressed genes without a priori sequence information. Therefore, the investigator's aim is to use this technology to identify mRNAs that increase in olfactory epithelia during massive, synchronous neurogenesis of olfactory receptor neurons. This will include identifying mRNAs that are differentially abundant between early and intermediate stages in the process of neurogenesis. These experiments have the potential to: 1) identify a significant fraction of the genes involved in neurogenesis of olfactory receptor neurons; 2) identify signaling pathways that regulate neurogenesis; 3) expand the number of markers of cell types in the olfactory receptor neuron lineage; and 4) identify previously unknown cell types in the lineage. Within olfaction, the experiments have implications for embryonic development of the olfactory epithelium, for olfactory carcinomas, for regeneration, and aging processes in the olfactory epithelium. The experiments also have implications for neurogenesis in adult mammals in general, including using this knowledge to develop interventions in neurodegenerative disorders and traumatic injury to the nervous system.

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