Abstract
Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of "twist" circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.
Original language | English |
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Article number | 1062 |
Pages (from-to) | 1062 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - Dec 1 2018 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry,Genetics and Molecular Biology
- General Physics and Astronomy
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In: Nature Communications, Vol. 9, No. 1, 1062, 01.12.2018, p. 1062.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The choroid plexus is an important circadian clock component
AU - Myung, J.
AU - Schmal, C.
AU - Hong, S.
AU - Tsukizawa, Y.
AU - Rose, P.
AU - Zhang, Y.
AU - Holtzman, M.J.
AU - De Schutter, E.
AU - Herzel, H.
AU - Bordyugov, G.
AU - Takumi, T.
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PY - 2018/12/1
Y1 - 2018/12/1
N2 - Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of "twist" circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.
AB - Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of "twist" circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.
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U2 - 10.1038/s41467-018-03507-2
DO - 10.1038/s41467-018-03507-2
M3 - Article
SN - 2041-1723
VL - 9
SP - 1062
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1062
ER -