The olfactory epithelium has a remarkable ability to regenerate. The experiments I propose here outline a method for using microarrays to profile transcription during neurogenesis in the olfactory system after lesion-induced death of the ORNs and their progenitors. The olfactory epithelium is an excellent system in which to study neurogenesis for a number of reasons. Neurogenesis has been shown to occur in a well-characterized and reproducible manner following removal of the olfactory bulb or lesions to the olfactory epithelium. It also occurs in a fairly synchronized fashion, with specific genes expressed at different time points through the course of the process. Moreover, this tissue has been extensively characterized, and contains well-defined cell populations that can be readily distinguished using antibodies to cell-type specific markers. These features should allow me to profile neurogenesis at discrete time points over the course of neuronal development from progenitor cells in vivo. Once I have identified a set of potential candidate genes through the statistical methods outlined, I will use RNA in situ hybridization analysis to confirm their expression during neurogenesis, and to localize it to specific olfactory epithelial cell types. My long term objective is to use the olfactory epithelium as a model to understand neurogenesis. This research may provide insight into regenerative therapies to treat neural degenerative diseases, and neural injuries.
