Achieving singularity in mammalian odorant receptor gene choice.

Odor discrimination requires differential expression of odor detectors. In fact, olfactory input to the brain is organized in units (glomeruli) innervated only by olfactory sensory neurons that express the same odorant receptor (OR). Therefore, discriminatory capacity is maximized if each sensory neuron expresses only one allele of a single OR gene, a postulate sometimes canonized as the "one neuron-one receptor rule." OR gene choice appears to result from a hierarchy of processes: differential availability of the alleles of each OR gene, zonal exclusion (or selection), OR gene switching during the initiation of OR gene transcription, and OR-dependent feedback to solidify the choice of one OR gene. The mechanisms underlying these processes are poorly understood, though a few elements are known or suspected. For example, the mechanism of activation of OR gene transcription appears to work in part through a few homeobox transcription factors (Emx2, and perhaps Lhx2) and the Ebf family of transcription factors. Further insights will probably come from several directions, but a promising hypothesis is that epigenetic mechanisms contribute to all levels of the hierarchical control of OR gene expression, especially the repressive events that seem to be necessary to achieve the singularity of OR gene choice.