The sense of smell (olfaction) is designed to detect a very wide variety of chemical structures in the external environment. In the mouse, chemosensory detection at the molecular receptor level is mediated primarily by a repertoire of ~1,100 odorant receptor (OR) genes expressed in olfactory sensory neurons (OSNs) in the main olfactory epithelium. These ORs have the seven-transmembrane structure that is typical for G-protein coupled receptors. Each mature OSN is thought to express just one OR gene, and only one of the two alleles of that OR gene. Axons of OSNs that express the same OR gene terminate and coalesce into a few glomeruli, which are well-delinead anatomical structures in the olfactory bulb numbering ~3,600 in an adult mouse. What are the molecular mechanisms that enable an OSN to restrict expression of the immense OR gene repertoire to just one gene and one allele of it? What are the molecular and cellular mechanisms that enable axons of OSNs that express the same OR gene to coalesce with high precision into glomeruli? We are approaching these fundamental biological questions by genetic manipulation of the mouse.
