The development of the olfactory system and the regulation of odorant receptor genes

Specificity of odorant detection depends upon the binding of odorous ligands to receptors on the cilia of olfactory sensory neurons. Olfactory neurons obtain the specificity of their odorant response by expressing a few or perhaps only one receptor gene from a large multigene family of odorant receptors. How are these genes regulated, such that a neuron selects for expression a particular gene or genes from this family? These questions were addressed in a study of the zebrafish olfactory system. Our results demonstrate that olfactory neurons do not stochastically activate an odorant receptor gene from the multitude of possible receptor genes during embryonic development. Thus, odorant receptor genes are specifically regulated in a time-dependent manner as the olfactory system matures. By evaluating the expression pattern of a receptor gene subfamily in adult olfactory neurons, we observe that closely related genes are not expressed in the same cell. This mechanism maximizes an organism's ability to discriminate between odors, and the advantage conferred by this ability was likely to have been a driving force in the expansion of the odorant receptor gene repertoire. Some current models of receptor gene regulation that relate genomic organization to receptor gene expression were evaluated. We found that receptor genes that lie clustered within the genome are regulated differently, as they are expressed at different developmental timepoints and are not expressed in the same mature olfactory neurons. Finally, a cell-autonomous model for odorant receptor gene regulation during development is proposed, whereby olfactory neurons may activate a subset of receptors for expression based on the number of mitotic divisions a precurser cell has undergone.