ИСТИНА

The mammalian circadian timing system consists of a central pacemaker in the brain’s suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN synchronizes peripheral clocks through a variety of systemic signals. While feeding rhythms are the most dominant Zeitgebers for most peripheral oscillators, the SCN also employs blood-borne and body temperature-dependent signals to set the phase in peripheral tissues. In the first part of the talk I will address the issue of how the SCN and feeding rhythms synchronize circadian oscillators in the liver. To this end we engineered the RT-Biolumicorder, a device enabling us to record circadian gene expression in the liver of freely moving mice during months. Using this approach, we can readily determine the kinetics of phase shifting, a parameter that is much more sensitive to the disruption of an individua l signalling pathway than the steady-state phase. The results indicate that the SCN uses both indirect pathways (depending on rest-activity cycles and feeding rhythms) and more direct (feeding-independent pathways) to synchronize liver clocks. Moreover, our studies suggest that hepatocyte clocks are strongly coupled between cells and that their synchronization immediately follows the phase of the SCN upon changing the light-dark regimen. In the second part of my talk I will present transcriptional and posttranscriptional pathways by which cyclically active blood-borne signals, cytoskeleton dynamics, and body temperature rhythms determine the amplitude, magnitude, and phase of circadian gene expression in peripheral tissues.