Mechanisms of cell birth and death in the adult olfactory epithelium

The Olfactory Epithelium (OE) possesses the rare ability among adult mammalian neuronal tissue to regenerate after damage. Remarkably, cell regeneration in the OE is rarely accompanied by tumors that would indicate uncontrolled cell proliferation (Bailey and Barton 1975; Bouhamdan et al. 2004). This tightly regulated regenerative capability of the OE is mainly due to the presence of progenitor cells that become mitotic upon extensive OE cell damage but exit the cell cycle once their progeny differentiate and replenish OE cell numbers. Additionally, induction of olfactory neuron apoptotic cell death through bulbectomy results in a stereotypic expansion of the mitotic population of progenitor cells in the OE. Once these dividing cells produce neurons, the number of proliferating cells decrease. Thus it is clear that regeneration involves the delicate balance and interaction of proliferation, differentiation and cell survival. Understanding of adult OE regeneration has been limited by the fact that the adult system cannot be reconstituted in culture. Olfactory neurons undergo precocious cell death in vitro , and progenitor cells only undergo a few rounds of cell division (Feron et al. 1999). As a result, the molecular mechanisms for the regulation of adult OE progenitor cell proliferation remain largely unknown.; The present set of studies attempt to rescue olfactory neurons from cell death in vitro. These studies also attempt to utilize genetic microarray technology to obtain a comprehensive gene expression profile of regenerating OE to further identify molecular factors and pathways that may mediate OE regeneration. Temporal gene expression patterns obtained from microarray analysis were further correlated with spatial expression within the major cell types of the OE. The patterns generated suggest a previously unknown heterogeneity among immature neurons in the OE. Temporal expression patterns were further used to identify receptor ligand pairs with reciprocal expression that would suggest functional roles in OE regeneration. We specifically look at the role of FGFs in the OE. Unique expression patterns for these growth factors and their receptors indicate a novel role for FGF9.