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

Abstract

In the mouse olfactory system, there are ~1500 odorant receptor (OR) genes clustered at ~50 different loci which are scattered among most of the chromosomes (Buck and Axel, 1991; Zhang and Firestein, 2002; Godfrey et al., 2004). Like the antigen receptor genes in lymphocytes, the mammalian OR genes are expressed in a mutually exclusive (Malnic et al., 1999; Serizawa et al., 2000) and monoallelic (Chess et al., 1994; Ishii et al., 2001) manner in olfactory sensory neurons (OSNs). DNA rearrangement has long been thought of as a possible mechanism for the allelic exclusion of the OR genes. However, mice cloned with OSN nuclei excluded the possibility of irreversible gene translocation as a mechanism to activate a single OR gene in each OSN (Eggan et al., 2004; Li et al., 2004). How is it, then, that allelic exclusion is achieved in the olfactory system? Since OSNs expressing a given OR gene converge their axons to a specific set of projection sites (glomeruli) on the olfactory bulb (OB) (Ressler et al., 1994; Vassar et al., 1994; Mombaerts et al., 1996; Feinstein and Mombaerts, 2004), odorous stimuli received in the olfactory epithelium (OE) are converted to a topographic map of activated glomeruli on the OB (Mori et al., 1999). Thus, the one neuron–one receptor rule forms the genetic basis for OR-instructed axonal projection of OSNs. Here, we discuss possible mechanisms that regulate single OR gene expression in each OSN in mouse.