A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset ofolfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system. The olfactory system combines broad selectivity with extreme sensitivity for the detection and discrimination of a large number of odorants. A combination of two cellular mechanisms might form the basis for odor discrimination: (i) selectivity by a limited set of olfactory receptors in each sensory neuron and (ii) spatio-temporal patterns of action potentials in cells projecting from the olfactory epithelium to the olfactory bulb. In vertebrates, odorants exert their actions by modulating the excitability of sensory neurons located in an epithelium in the nasal airways (1-4). Peripheral odor-induced activity is transmitted directly to the mitral cells in the olfactory bulb where it is integrated and relayed to other regions in the central nervous system (CNS) (5). Olfactory cilia on the apical ends of neuronal dendrites are embedded in a mucus layer that separates the olfactory epithelium from the external air. Signal transduction is initiated when odorants interact with specialized receptors in the ciliary membranes (6-8). In vitro, odorants can rapidly stimulate guanine nucleotide binding (G) protein-coupled second messenger pathways for both cAMP and inositol trisphosphate (9), suggesting that at least two classes of G-protein-coupled receptors are expressed by olfactory neurons. A group of 10-18 candidate olfactory receptors that appear to define a class in the G-protein-coupled receptor superfamily was identified in the olfactory epithelium (10). The tissue specificity and the large number of genes for these receptors suggest that they are responsible for the detection of numerous odorants, a hypothesis that awaits confirmation. Recently, members of a putative olfactory receptor gene family have been identified in mammalian germ cells, suggesting a broader range of function for these receptors (11).To understand the molecular and cellular basis of odor discrimination, we adopted a strategy to isolate olfactoryspecific receptor genes and to study their expression in the olfactory epithelium. In this report, we have characterized a G-protein-coupled receptor (OR3) ¶ and its gene expression.The OR3 pattern of expression is symmetric within and specific to the olfactory epithelium. We present evidence that the first OR3-positive cells appear to originate from the CNS, suggesting that this receptor might serve a functional role not only in odor coding but also in the elaboration ...