Regulation of tissue regeneration by the circadian clock

Apr 24, 2021The European journal of neuroscience

How the body’s internal clock controls tissue repair

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Abstract

Circadian rhythms maintain approximately 24-hr periodicity in biological processes.

Circadian timing influences various cellular behaviors that support tissue regeneration.
Clock gene products are essential for proper DNA synthesis and cell cycle progression.
Elements of the cell cycle can feedback and impact circadian timing mechanisms.
Crosstalk between the circadian system and the cell cycle regulates stem cell proliferation and differentiation.
Circadian control is linked to tissue homeostasis and repair.

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Circadian rhythms are regulated by a highly conserved transcriptional/translational feedback loop that maintains approximately 24-hr 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 behaviours 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 feedback 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 signalling 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.

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Regulation of tissue regeneration by the circadian clock

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