TY - JOUR
T1 - The choroid plexus is an important circadian clock component
AU - Myung, Jihwan
AU - Schmal, Christoph
AU - Hong, Sungho
AU - Tsukizawa, Yoshiaki
AU - Rose, Pia
AU - Zhang, Yong
AU - Holtzman, Michael J.
AU - De Schutter, Erik
AU - Herzel, Hanspeter
AU - Bordyugov, Grigory
AU - Takumi, Toru
N1 - Funding Information:
We thank N. Nakagawa for providing guidance on gap junction blockers, T. Suzuki and K. Yamakawa for introducing FOXJ1-Cre, J. Harrison and C. Harrison for critical reading of the manuscript, and S.D. Aird for editorial support. This work has been supported by Strategic Japanese–German Cooperative Program from the Japan Science and Technology Agency and the Deutsche Forschungsgemeinschaft (BO 3612/2-1), Grant-in-Aid for Scientific Research (16H01652, 16H06463) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, Grant-in-Aid for Scientific Research (16K08538, 15K06715, 25242077, 16H06316, 16K13110) from the Japan Society for the Promotion of Science and the Taiwan Ministry of Science and Technology Grants (104–2420-H-038–001-MY3, 106–2632-H-038–001). J.M. acknowledges additional supports from the Wissenschaftskolleg zu Berlin and Einstein Foundation Berlin (BAK-F1–2017). C.S. acknowledges support from the Joachim Herz Stiftung. S.H. and E.D.S. are supported by OIST Graduate University. M.J.H. is supported by NIH NHLBI R01-AI130591.
Publisher Copyright:
© 2018 The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85044173112&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03507-2
DO - 10.1038/s41467-018-03507-2
M3 - Article
C2 - 29540683
AN - SCOPUS:85044173112
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1062
ER -