Development of the Circadian Core Machinery in Mammals.

The emergence of circadian molecular oscillation is observed as a gradual process during the development in mammals. Pluripotent stem cell differentiation cultures recapitulate this process, whereas reprogramming into an undifferentiated state reverses it. These findings indicate that the circadian clock is tightly coupled to the state of cellular differentiation. The state of the circadian core machinery in nonrhythmic cells may be different from that in rhythmic cells. In this review, we describe the circadian rhythm development during ontogeny in mammals and focus on the molecular mechanisms that suppress circadian molecular oscillations during early development and in pluripotent stem cells. We also discuss the biological implications of repressing cellular circadian oscillation in nonrhythmic cells.