The Tissue Clock Network: Driver and Gatekeeper of Circadian Physiology

In mammals, a network of cellular circadian clocks organizes physiology and behavior along the 24-h day cycle. The traditional hierarchical model of circadian clock organization with a central pacemaker and peripheral slave oscillators has recently been challenged by studies combining tissue-specific mouse mutants with transcriptome analyses. First, a surprisingly small number of tissue rhythms are lost when only local clocks are ablated and, second, transcriptional circadian rhythms appear to be regulated by a complex mix of local and systemic factors. As reviewed here, these findings suggest a more integrated model of clock network interaction with the central pacemaker as the main source of behavioral and systemic-physiological rhythms and peripheral clocks controlling some local rhythms while at the same time acting as gatekeepers that temporally adjust cellular responses to external stimuli.