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The bird olfactory system has a simple structure and affords an attractive developmental model for the study of olfactory morphogenesis and differentiation. We have cloned and characterized several chick olfactory receptor (COR) genes belonging to the superfamily of seven-transmembrane domain proteins. In situ hybridization analysis of their spatiotemporal patterns of expression during development reveals several important characteristics. COR expression starts early in placodal cells (Embryonic Day 5, E5). Changes in their expression pattern then correlate with the onset of synaptogenesis (E8). The adult pattern, achieved before hatching, shows that cells expressing a particular COR are not regionalized within the epithelium. By double-label in situ hybridization, we clearly demonstrate that a single cell does not coexpress different COR genes (or subsets of CORs) at any stage of development. Following bulbar deafferentation, COR expression ceases more rapidly than expected from previous axotomy experiments. Concomitantly, a reactivation of the Cash-1 gene, which is involved in early neuronal specification, could be an early sign of olfactory neuronal regeneration. Modulation of COR and Cash-1 expression points to a simultaneous process of neuronal degeneration and regeneration in the olfactory epithelium after axotomy. COR expression is restricted to the olfactory epithelium except during early stages (before synaptogenesis). At that time, cells distributed along the olfactory nerve, from the placode to the anterior telencephalon, also express CORs. This cell population is different from the luteinizing hormone releasing hormone neurons migrating from the placode. Our results show that the olfactory neurons or neuroblasts choose to express one COR before establishing functional connections with the bulb. Later on, bulboepithelial connections seem important not only for olfactory neuron survival but also for stimulation of COR expression. In addition, beyond their implication in functional odor detection, CORs could be involved, at early stages, in processes of olfactory morphogenesis, including the establishment of a bulbar chemotopy.