Gene Switching and the Stability of Odorant Receptor Gene Choice

Abstract

Individual olfactory sensory neurons express only a single odorant receptor from a large family of genes, and this singularity is an essential feature in models of olfactory perception. We have devised a genetic strategy to examine the stability of receptor choice. We observe that immature olfactory sensory neurons that express a given odorant receptor can switch receptor expression, albeit at low frequency. Neurons that express a mutant receptor gene switch receptor transcription with significantly greater probability, suggesting that the expression of a functional odorant receptor elicits a feedback signal that terminates switching. This process of receptor gene switching assures that a neuron will ultimately express a functional receptor and that the choice of this receptor will remain stable for the life of the cell.

Activity plays a role in eliminating olfactory sensory neurons expressing multiple odorant receptors in the mouse septal organ

“…This result lends support to the second and/or third possibility, but further experiments will be required to distinguish them. In addition to the mechanisms proposed in OR gene selection and stabilization (Fuss et al, 2007;Lewcock and Reed, 2004;Lomvardas et al, 2006;Nguyen et al, 2007;Serizawa et al, 2003;Shykind et al, 2004), the current study reveals an activity-dependent mechanism in ensuring and maintaining that one cell expresses only receptor in a subset of sensory neurons.…”

“…This may result from the higher frequency of receptor gene switching at early developmental stages (Shykind et al, 2004). Alternatively, this may represent expression "errors" occurring randomly (Mombaerts, 2004), which can be corrected during postnatal development.…”

“…The second possibility is that one of the coexpressed odorant receptors, favorably stimulated by the olfactory cues, becomes dominant in that neuron by suppressing the others via a negative feedback mechanism (Lewcock and Reed, 2004;Serizawa et al, 2003;Shykind et al, 2004). The third possibility is that the OSNs maintain the capability to switch their receptor selection even in adulthood, and the switching only stops when the neuron is functionally activated and one selection is thus stabilized.…”

“…If the sensory activity indeed plays a role in ensuring the singular expression pattern in some OSNs as we proposed, we would expect that coexpression occurs at a higher frequency in early developmental stages when the OSNs have little olfactory experience and a higher chance of switching the receptor selection (Shykind et al, 2004). We examined the coexpression frequency in the septal organ from newborn mice (at postnatal day 0).…”

“…The underlying mechanism is under extensive investigation and likely involves several hierarchical steps from the initial OR selection to silencing other ORs (Fuss et al, 2007;Lomvardas et al, 2006;Nguyen et al, 2007). It has been reported that stabilizing an OR choice in individual neurons requires a negative feedback triggered by the receptor protein, especially encoded by a functional OR gene (Lewcock and Reed, 2004;Serizawa et al, 2003;Shykind et al, 2004). Here we hypothesize that the neuronal activity elicited by sensory stimulation plays a role in ensuring the one neuron-one receptor tenet.…”