Decision letter: Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant

Abstract

Jet lag is a common experience when flying long distance. This disorientating phenomenon occurs when our internal ‘body clock’ remains set to the time zone where the plane departed and fails to reset to the new local time. Our internal clock actually consists of a series of clocks—each of which is based upon groups of genes that are switched on and off at different times of the day and night. There is a master clock in our brain and a series of peripheral clocks in our other organs and tissues. The master clock is thought to coordinate the peripheral clocks, which in turn control the fluctuating activity of a specific organ in response to the time of day. To further investigate the master clock, a typical approach has been made to disable it by deleting the genes for its components. But some of these deletions can cause abnormalities in mice and some are lethal. To get around these problems, Izumo, Pejchal et al. have devised a way to delete a molecular component of the master clock only in the mouse's brain. Izumo, Pejchal et al. used this approach to specifically disable the mouse's master clock and, unlike mice that completely lack the Bmal1 gene, mice with the brain-specific deletion were as healthy and lived as long as normal mice. A molecular probe was used to monitor the peripheral clocks in different organs and tissues of these mutant mice, and revealed that, without a working master clock, the peripheral clocks were no longer synchronized. Izumo, Pejchal et al. found that the lost synchrony could be partially restored by training the mice to adapt to cycles of light and dark and feeding schedules. Following on from the work of Izumo, Pejchal et al., one of the next challenges is to understand how the master clock communicates with the peripheral clocks in different organs and tissues around the body.