Regulation of tissue regeneration by the circadian clock.

Circadian rhythms are regulated by a highly conserved transcriptional/translational feedback loop that maintains approximately 24-hour periodicity from cellular to organismal levels. Much research effort is being devoted to understanding how the outputs of the master clock affect peripheral oscillators, and in turn, numerous biological processes. Recent studies have revealed roles for circadian timing in the regulation of numerous cellular behaviors in support of complex tissue regeneration. One such role involves the interaction between the circadian clockwork and the cell cycle. The molecular mechanisms that control the cell cycle create a system of regulation that allows for high fidelity DNA synthesis, mitosis, and apoptosis. In recent years, it has become clear that clock gene products are required for proper DNA synthesis and cell cycle progression, and conversely, elements of the cell cycle cascade feed back to influence molecular circadian timing mechanisms. It is through this crosstalk that the circadian system orchestrates stem cell proliferation, niche exit, and control of the signaling pathways that govern differentiation and self-renewal. In this review, we discuss the evidence for circadian control of tissue homeostasis and repair and suggest new avenues for research.