Light can synchronise peripheral clocks autonomously from each other

Organisms have adapted to the changing environmental conditions within the 24h cycle of the day by temporally segregating tissue physiology to the optimal time of the day. On the cellular level temporal segregation of physiological processes is established by the circadian clock, a Bmal1 dependent transcriptional oscillator network. The circadian clocks within individual cells of a tissue are synchronised by environmental signals, mainly light, in order to reach temporally segregated physiology on the tissue level. However, how light mediated synchronisation of peripheral tissue clocks is achieved mechanistically and whether circadian clocks in different organs are autonomous or interact with each other to achieve rhythmicity is unknown. Here we report that light can synchronise core circadian clocks in two peripheral tissues, the epidermis and liver hepatocytes, even in the complete absence of functional clocks in any other tissue within the whole organism. On the other hand, tissue extrinsic circadian clock rhythmicity is necessary to retain rhythmicity of the epidermal clock in the absence of light, proving for the first time that the circadian clockwork acts as a memory of time for the synchronisation of peripheral clocks in the absence of external entrainment signals. Furthermore, we find that tissue intrinsic Bmal1 is an important regulator of the epidermal differentiation process whose deregulation leads to a premature aging like phenotype of the epidermis. Thus, our results establish a new model for the segregation of peripheral tissue physiology whereby the synchronisation of peripheral clocks is acquired by the interaction of a light dependent but circadian clock independent pathway with circadian clockwork dependent cues. Determining the epidermal circadian transcriptome in the presence or absence of non-epidermal clocks under light entrainment (LD).生物体可通过将组织生理活动分配至每日最优时段，适应24小时昼夜周期内不断变化的环境条件。在细胞层面，生理过程的时间分区由昼夜节律时钟（circadian clock）构建，这是一类依赖Bmal1的转录振荡网络。组织内单个细胞中的昼夜节律时钟会通过环境信号（主要为光照）实现同步，进而在组织层面达成时间分区的生理状态。但目前尚不明确光照介导的外周组织生物钟同步的具体机制，也不清楚不同器官的生物钟是自主运作还是相互协作以产生节律。 本研究发现，即便整个生物体的其他所有组织均无功能性生物钟，光照仍可同步两种外周组织——表皮与肝脏肝细胞的核心昼夜节律时钟。此外，在无光照条件下维持表皮生物钟的节律性，需要来自其他组织的外源性生物钟节律，这首次证实生物钟系统可作为时间记忆，在无外部授时信号时实现外周生物钟的同步。同时我们发现，组织内源性的Bmal1是表皮分化过程的重要调控因子，其失调会导致表皮出现早衰样表型。 综上，本研究结果为外周组织生理的时间分区建立了全新模型：外周生物钟的同步可通过依赖光照但不依赖生物钟的通路，与依赖生物钟系统的信号之间的相互作用实现。本研究还在光照授时（光暗周期，LD）条件下，分别测定了存在与不存在非表皮生物钟时的表皮节律性转录组。