Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice
Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. We found in vitro and in vivo a robust diurnal rhythm of Rev-Luc, mainly in liver, intestine, kidney and adipose tissues. We further confirmed in vivo that Rev-Luc peripheral tissues are food-entrainable oscillators, not affected by age or sex. These data strongly support the relevance of the Rev-Luc model for circadian studies, especially to investigate in vivo the establishment and the entrainment of the rhythm throughout ontogenesis. We then showed that Rev-Luc expression develops dynamically and gradually, both in amplitude and in phase, during fetal and postnatal development. We also demonstrate for the first time that the immature peripheral circadian system of offspring in utero is mainly entrained by maternal cues from feeding regimen. The prenatal entrainment will also differentially determine the Rev-Luc expression in pups before weaning underlining the importance of the maternal chrononutrition on the circadian system entrainment of the offspring.
KeywordsRev-erbα Bioluminescent imaging In utero Ontogenesis Feeding cues Circadian clock
We acknowledge the contribution of the SFR Biosciences UMS3444 animal facility PBES. We gratefully thank N. Aguilera and C. Coutanson for their technical assistance and K. Gauthier for her manuscript comments. This work was supported by the European Commission Grants FP6 CRESCENDO LSHM-CT-2005-01865 (JS, FD); the Agence Nationale de la Recherche; CHRONOMET Project ANR-12-BSV1-0014-01 (FD) and LABEX SIGNALIFE program ANR-11-LABX-0028-01 (FD).
LC designed, performed and analyzed all the experiments. AGC and FD designed the vector and performed the experiment (Fig. 1b). ODB performed the experiment (Fig. 1e) and the cosinor analyses. JS supervised the work. LC, ODB and JS wrote the manuscript.
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Conflict of interest
The authors declare no competing financial interests.
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