EARLY EVENTS IN OLFACTION - DIVERSITY AND SPATIAL PATTERNS OF ODORANTRECEPTORS

In the past few years, a major advance was made in understanding early events in olfaction. In particular, a molecular basis for the sense o f smell has emerged. I will focus on the most recent data obtained on an extremely large subfamily of putative odorant receptors. These resu lts may explain how the olfactory system can recognize and distinguish thousands of odoriferous molecules and how the spatial coding of odor molecules could be generated in the olfactory epithelium and subseque ntly transmitted to the olfactory bulb. The putative odor receptors ar e a subfamily of seven-transmembrane-domain G protein-coupled receptor s; although their functions have not yet been definitively proven, the y may act as odor receptors. This new receptor gene family has the fol lowing characteristics: 1) It is a multigene family of phylogeneticall y related sequences consisting of approximately 100 members in fish an d up to approximately 1000 members in rodents. 2) Members of this fami ly are expressed in the olfactory epithelium (olfactory receptors). Re lated genes are expressed in the gustatory epithelium of the tongue (g ustatory receptors), and in sperm cells (germ-cell receptors). 3) Gene s for the olfactory receptor family have been isolated from several sp ecies including fish, rat, mouse, human and chick. 4) Olfactory recept or protein seems to be localized on the ciliary surface of olfactory n eurons. 5) On the basis of a reconstitution experiment, olfactory rece ptors exhibit broad ligand specificity. 6) A single receptor is expres sed in only 0.1%-2% of the entire olfactory neuron population. 7) A si ngle olfactory neuron expresses only a subset of the entire receptor g ene repertoire. 8) The spatial distribution of individual receptors on the surface of the olfactory epithelium is random in fish but segrega ted with bilateral symmetry in rodents. 9) Based on a developmental st udy, some members of the olfactory receptor family are expressed in th e developing mouse olfactory epithelium as early as embryonic day E12. 10) In mice at E10, the receptor designated OR3 was not found in the progenitor cells of olfactory neurons in the olfactory placode, but wa s found in neural crest cells, suggesting a central origin for some ol factory neurons. These results together with their functional implicat ions and several hypotheses concerning basic events in olfaction will be discussed.