UC Irvine

The neuronal lineage of the olfactory epithelium (OE) is a cell lineage that includes the neuronal stem cell and its progeny (ultimately the mature olfactory receptor neuron [ORN]). Recent studies, including further characterization of the neuronal lineage of the OE, and of factors that influence proliferation, survival, and death of cells of this lineage, have contributed significantly to understanding of neuronal homeostasis, i.e., normal maintenance of neuronal number, in mammalian OE. Our recent studies indicate that in adult mice, all cell types of the neuronal lineage of the OE-neuronal precursors, immature ORNs and mature ORNs-undergo constitutive death, i.e., a normal, basal level of cell death, that is characteristic of programmed cell death or apoptosis. To some extent, constitutive cell death in this lineage may reflect random environmental insults; however, this may also be the result of an ongoing developmental program that acts to control both numbers and phenotypic organization of olfactory neurons. Although a variety of extrinsic and intrinsic factors are likely to contribute to cell death in the neuronal lineage of the OE, most have not been thoroughly studied. Detailed analysis of one of these factors, effects of target deprivation, suggests that survival of individual cell types of the neuronal lineage of the OE may be differentially regulated with mature ORNs, but not immature ORNs or neuronal precursors, dependent upon the olfactory bulb for their survival. Factors normally provided to cells of the ORN lineage, as in other neuronal systems, are likely to promote survival by inhibiting an endogenous genetic program of cell death. Whether candidate polypeptide growth factors, e.g., the neurotrophins, or other pharmacological inhibitors ofapoptosis will eventually play a role in the treatment of specific anosmias remains to be deter-mined.