Odorant and pheromone receptor gene regulation in vertebrates

The largest mammalian gene family codes for odorant receptors and is exclusively devoted to the perception of the outside world. Its expression is very peculiar, since olfactory sensory neurons are only allowed to express a single of its numerous members, from a single parental allele. How this is achieved is unknown, but recent work points to multiple regulatory mechanisms, possibly shared by pheromone receptor genes, acting at (a) a general level, via the expression of the chemoreceptor itself and (b) a more restricted level, defined by activator elements.

Introduction

All life forms need tools to adequately respond to the known and unknown surroundings. These tools must bear a series of sensors whose diversity and complexity allows the high discrimination power the individual may necessitate. Multiple options, some of them remarkably creative, have been selected by evolution to achieve sensor variability. The mammalian immune system, for example, which encounters pathogens when the latter invade its territory, evolved a strategy breaking the dogma of genomic integrity, thus drastically increasing lymphocyte receptor diversity [1]. A very similar challenge is faced by olfactory sensory neurons: they constantly probe the outside world, part of which has never been experienced. Unlike immune cells, olfactory sensory neurons do not base their strategy on recombination to generate sensor diversity, but instead dispose a genomic repertoire of receptor genes of amazing size, from which they can choose from [2, 3].

The two major mammalian olfactory neuronal circuits, the main olfactory and vomeronasal systems, are functionally and physically separate. Their sensory neurons express seven transmembrane receptors to sense the world. Odorant receptors (ORs) are expressed by olfactory neurons from the main system, while vomeronasal neurons express pheromone receptors of the V1R or V2R type (which do not share sequence homologies with ORs or between each other). One hundred and ninety-one V1R [4^•] and 70 V2R [5] genes have been identified in the mouse, while the OR repertoire size is up by an order of magnitude [6].

Every olfactory sensory neuron expresses a single olfactory receptor gene, from a single allele, which results in hundreds of functionally different neuronal populations in the nasal cavity [2, 3, 7, 8, 9, 10, 11, 12]. This view, involving thousands of narrowly tuned parallel lines, is at the base of our current understanding of olfactory coding at the peripheral level. How each sensory neuron is able to exclusively transcribe a single olfactory receptor gene is unknown. However, recent observations in the mouse suggest the existence of multiple levels of regulation, both at the gene, at the gene cluster, and at more global levels; these will be discussed here.