Regulation of odorant receptors: one allele at a time

The odorant receptors (ORs) make up the largest gene family in mammals. Each olfactory sensory neuron chooses just one OR from the more than 1000 possibilities encoded in the genome and transcribes it from just one allele. This process generates great neuronal diversity and forms the basis for the development and logic of the olfactory circuit between the nose and the brain. The mechanism behind this monoallelic regulation has been the subject of intense speculation and increasing experimental investigation, yet remains enigmatic. Recent genetic experiments have brought the outlines of the process into sharper relief, identifying a feedback mechanism in which the first odorant receptor expressed, generates a signal that stabilizes its choice, thus maintaining singular selection. In the absence of this signal, the olfactory neuron re-enters the selection process and switches to choose an alternate OR. Irreversible genetic changes in the nuclei of olfactory neurons do not accompany OR selection, which must therefore be initiated by an epigenetic process that may involve a stochastic mechanism.