Development of circadian rhythms in mammalian systems

In mammals, molecular mechanisms of circadian rhythms involve a time-delayed negative feedback loop generating autonomous oscillations of ∼24 h. Most cell types in mammals possess circadian rhythms regulating temporal organization of cellular and physiological processes. Intriguingly, pluripotent stem cells do not possess circadian rhythms and oscillations arise after a defined period of differentiation. Previous studies demonstrated that post-transcriptional regulations of core clock components, CLOCK and PER2, play critical roles in inducing circadian rhythms. In this article, we review the development of circadian rhythms in mammalian systems and provide a theoretical understanding of potential mechanisms regulating the birth of circadian rhythms using mathematical modeling.