Genome-wide screen reveals rhythmic regulation of genes involved in odor processing in the olfactory epithelium. Mus musculus

Odor discrimination behavior displays circadian fluctuations in mice indicating that mammalian olfactory function is under control of the circadian system. This is further supported by the facts that odor discrimination rhythms depend on the presence of clock genes and that olfactory tissues contain autonomous circadian clocks. However, the molecular link between circadian function and olfactory processing is still unknown. In order to elucidate the molecular mechanisms underlying this link, we focused on the olfactory epithelium (OE), the primary target of odors and the site of the initial events in olfactory processing. We asked whether olfactory sensory neurons (OSNs) within the OE possess an autonomous circadian clock and whether olfactory pathways are under circadian control. Employing clock gene-driven bioluminescence reporter assays, immunohistochemistry and a time-dependent microarray-based transcriptome analysis on OE samples, we found robust circadian rhythms of core clock genes and their proteins in OSNs, suggesting that the OE indeed contains an autonomous circadian clock. Furthermore, we identified several OSN-specific components of the olfactory pathway that are under circadian control, including several candidates with putative roles in circadian olfactory processing, such as KIRREL2 -- an established factor involved in short-term OSN activation. The spatiotemporal expression patterns of our candidate proteins suggest that they are involved in short-term anabolic processes to rhythmically prepare the cell for peak performances and to promote circadian function of OSNs. Overall design: We performed a genome-wide expression study with RNA from OE tissue extracted at 4-h intervals in constant darkness from previously entrained mice. Total RNA of four mice per sampling time was pooled in equal amounts.