Growth & Gene Expression in Primary Sensory Neurons

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DESCRIPTION (provided by applicant): Loss of function following injury to the central nervous system (CNS) is due to a failure of axons within the CNS to re-grow. This is in contrast to the peripheral nervous system (PNS) where re-growth occurs. Despite years of study, the mechanisms responsible for the ability of the PNS, but failure of the CNS to regenerate remain poorly understood. Recently, advances in gene expression technology have made it possible to screen and identify thousands of gene expression profiles simultaneously using high density DNA microarrays. Using this new technology, genes that appear to regulate neuronal growth have been identified, however, identification by microarrays is inadequate evidence to draw conclusions about functional significance. Further characterization of these putative growth associated genes (GAGs) is therefore required The aim of this study is to use the unique properties of dorsal root ganglion (DRG) neurons to validate and characterize putative GAGs identified by microarray analysis. Expression profiles of putative DRG GAGs that have the following characteristics will be examined (i) upregulated during development, (ii) down regulated or not expressed in adult, (iii) upregulated after peripheral injury, and (iv) not expressed or down regulated after a central lesion. The expression profiles of putative DRG GAGs will be validated by slot, Northern, and Western blots, immunocytochemistry, and by in situ hybridization to determine cellular localization. Genes that fulfill the criteria for a growth promoting GAG will be examined in vitro and in vivo for their ability to regulate axonal growth and regeneration after CNS injury. These results will increase our understanding of the reasons for failure of central regeneration and may offer novel therapeutic opportunities to treat CNS injuries.