Circadian clock in the fetal choroid plexus matures earlier than the suprachiasmatic nucleus clock

The development of circadian clocks and their roles in the fetal brain have not been explored. We found that the fetal choroid plexus (fChP) of the PER2::LUC mouse is rhythmic on embryonic day (E)13, which is earlier than the central clock in the suprachiasmatic nuclei. At this stage, the expression of clock genes and genes encoding amino acid and thyroid hormone transporters was rhythmic. Time-resolved omics analyses revealed rhythmic proteins in the fChP and fetal cerebrospinal fluid (fCSF), including proteins involved in proteasome-mediated protein degradation, as well as rhythmic amino acids and other polar metabolites and lipids in the fCSF. These were largely distinct from rhythmic proteins and metabolites in maternal CSF and serum, respectively. These results indicate that the ChP clock functions as the earliest oscillator in the fetal brain and may, at least partially, control rhythmic secretion of compounds into the fCSF needed for neurodevelopment.