Molecular clocks in mouse skin.
Clock genes in the skin exhibit day-night changes in expression; however, whether these changes are brought by external light or intrinsic mechanisms is unclear. In this study, we demonstrated that expression of the clock and clock-controlled genes showed robust rhythms in mouse skin under constant dark conditions, whereas these rhythms were completely lost in Cry1/Cry2 knockout mice lacking a molecular clock. At the cellular level, the main oscillatory protein in the mammalian molecular clock, PER2, was expressed in the nuclei of keratinocytes in the epidermis and hair follicles, with expression peaking at CT16 (subjective dusk), 4-8 hours after expression of its mRNA. These expression patterns in the skin stopped after the ablation of the central clock in the suprachiasmatic nucleus (SCN), which was not recovered even in animals housed in 12 hour-light/12 hour-dark conditions. These findings demonstrate that the intrinsic oscillating molecular clock exists in the epidermis, and that signaling from the SCN is essential for the maintenance of the epidermal clock, and cannot be compensated by external light.
Tanioka
Miki
M
Division of Dermatology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yamada
Hiroyuki
H
Doi
Masao
M
Bando
Hideki
H
Yamaguchi
Yoshiaki
Y
Nishigori
Chikako
C
Okamura
Hitoshi
H
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D017440:Photoperiod; D012621:Seasons; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D012879:Skin Physiological Phenomena; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D005420:Flavoproteins; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors