Genome-Wide Screen Reveals Rhythmic Regulation of Genes Involved in Odor Processing in the Olfactory Epithelium.
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. 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 and time-dependent immunohistochemistry 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 performed a circadian transcriptome analysis and identified several OSN-specific components that are under circadian control, including those 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.
Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Manjana
M
Saleh
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Karsten
K
Jürchott
Cluster of Excellence NeuroCure, Charité-Universtitätsmedizin Berlin, Berlin, Germany Department of Pharmacology and Toxicology, University Hospital Jena, Jena, Germany.
Sonja
S
Oberland
Department of Pharmacology and Toxicology, University Hospital Jena, Jena, Germany.
Eva M
EM
Neuhaus
Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Achim
A
Kramer
Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany ute.abraham@charite.de.
Ute
U
Abraham
D000818:Animals; D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics* / Q000528:radiation effects; D005786:Gene Expression Regulation; D007136:Immunoglobulins / Q000235:genetics; D008163:Luminescent Measurements; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009812:Odorants; D009831:Olfactory Mucosa / Q000502:physiology*; D009833:Olfactory Pathways / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D056950:Period Circadian Proteins / Q000235:genetics; D013997:Time Factors; D046888:Tissue Array Analysis
D007136:Immunoglobulins; D008565:Membrane Proteins; C546601:Neph3 protein, mouse; D056950:Period Circadian Proteins
PERIOD2; bioluminescence; circadian; immunohistochemistry; olfactory sensory neurons