The proposed experiments were designed to better characterize the progeny and activity of horizontal basal cells (HBCs) in the adult mouse olfactory (OE) under normal conditions and during damage-induced neuronal regeneration.
Specific Aim 1. Identify the progeny of HBCs. Expression of the bacterial lacZ gene will be driven by a promoter that, within the OE, is specific to HBCs.
Specific Aim 2. Characterize OE turnover in the adult mouse following perturbation of HBC-specific expression of brain derived neurotrophic factor (BDNF). We will analyze olfactory receptor neuron turnover and differentiation state in adult mice that either over-express BDNF in a HBC-specific manner or are HBC-specific BDNF knockouts.
Specific Aim 3. Characterize damage-induced OE regeneration in the adult mouse following perturbation of HBC-specific BDNF expression. We will analyze olfactory receptor neuron turnover and differentiation state following damage to the OE in adult mice that either over-express BDNF in an HBC-specific or are HBC-specific manner or are HBC-specific manner or are HBC-specific BDNF knockouts. These experiments should help to resolve a controversy regarding which basal cell population is the olfactory epithelium stem cell. Better understanding of the basal cell populations within the OE will also allow us to take new directions in the prevention and treatment of olfactory dysfunction.
