The choroid plexus is an important circadian clock
, Christoph Schmal
, Sungho Hong
, Yoshiaki Tsukizawa
, Pia Rose
, Yong Zhang
Michael J. Holtzman
, Erik De Schutter
, Hanspeter Herzel
, Grigory Bordyugov
& Toru Takumi
Mammalian circadian clocks have a hierarchical organization, governed by the suprachias-
matic 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 hier-
archy 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.
RIKEN Brain Science Institute (BSI), Wako 351-0198, Japan.
Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa
Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei 11031, Taiwan.
TMU-Research Center of Brain and
Consciousness, Taipei Medical University, Taipei 11031, Taiwan.
Laboratory of Braintime, Shuang Ho Hospital, New Taipei City 23561, Taiwan.
Theoretical Biology, Charité-Universitätsmedizin and Humboldt Universität, Berlin D-10115, Germany.
Department of Anatomy, Hiroshima University School
of Medicine, Hiroshima 734-8551, Japan.
Pulmonary and Clinical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
These authors contributed equally: Jihwan Myung, Christoph Schmal, Sungho Hong. Correspondence and requests for materials should be addressed to
J.M. (email: email@example.com) or to H.H. (email: firstname.lastname@example.org) or to T.T. (email: email@example.com)