Negative Feedback Regulation Ensures the One Receptor-One Olfactory Neuron Rule in Mouse

TLDR

In the mouse olfactory system, each olfactory sensory neuron expresses only one odorant receptor gene in a monoallelic, mutually exclusive manner, forming the genetic basis for OR‑instructed axonal projection to the olfactory bulb during development. The study identifies an upstream cis‑acting DNA region that activates the OR gene cluster and proposes that stochastic activation of a single OR gene coupled with negative feedback from its product is required to enforce the one‑receptor‑one‑neuron rule. The authors identified an upstream cis‑acting DNA region that activates the OR gene cluster, permitting expression of only one OR gene per cluster. Deletion of the expressed OR gene’s coding region or a natural frame‑shift mutation permits a second OR gene to be expressed.

Abstract

In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) gene in a monoallelic and mutually exclusive manner. Such expression forms the genetic basis for OR-instructed axonal projection of OSNs to the olfactory bulb of the brain during development. Here, we identify an upstream cis-acting DNA region that activates the OR gene cluster in mouse and allows the expression of only one OR gene within the cluster. Deletion of the coding region of the expressed OR gene or a naturally occurring frame-shift mutation allows a second OR gene to be expressed. We propose that stochastic activation of only one OR gene within the cluster and negative feedback regulation by that OR gene product are necessary to ensure the one receptor–one neuron rule.