The Development And Mechanism Of Circadian Rhythms In Mouse Liver

Circadian rhythms are present in organisms of various phylogeny, and ensure that vital functions to occur in an appropriate and precise temporal sequence and in accordance with cyclic environmental changes. The mammalian master clock is located in the suprachiasmatic nucleus (SCN). Current models of the molecular circadian clockwork in eukaryotic cells are based on transcription-translation feedback loops. At the level of individual tissues, genes expression rhythms are brough by the actions the local circadian clock and systemic cues.Although the circadian clock oscillation is present in many tissues and cells, it is difficult be detected in rodent fetal tissues. There is relatively little known about the circadian clock status and the maternal influence on these clocks during embryo development. To gain a comprehensive overview of the clock status in the mouse fetal liver during late gestation, we performed microarray analyses on the fetal liver tissues. As a result, in the fetal liver we did not observe obvious rhythms of key circadian genes expression and many other transcripts known to be rhythmically expressed in the adult liver. And the clock genes such as Clock, Bmall, Cry1and Nrldl were found to be expressed at lower relative levels in the fetal liver. However, about145transcripts were found to be rhythmically expressed in the fetal liver at low amplitude. And also16transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to express obvious rhythmicity and show synchronized daily fluctuations at high amplitudes. This results indicated that the fetal liver cells were under the influence if maternal cues related to energy status and feeding. Overall approximately1100transcripts were differentially enriched between the fetal and adult livers. These transcripts represent genes with cellular functions characteristic of distinct developmental stages. And the developmental differences in liver gene expression might have contributed to the differences in oscillation status and functional states of the cellular circadian clock between fetal and adult livers. Given this and the closely link between circadian clock and cellular metabolism has been recent discovered. We scheduled the feeding time of thepregnant mouse, and we want to do further investigation and to get more details about the status of the feta liver clock through this experiment.When the mother mice are under restricted feeding, the expression rhythms of several clock genes can be detected in fetal livers. Those rhythms, although of low amplitude, reversed their profiles under opposite feeding cycles. Interestingly, clock gene Bmall and some genes related to metabolism could show biphasic expression in the fetal livers, possibly as a result of the interactions between the unique in utero milieu and the fetal liver clock. Regular rhythms of clock gene expression were detected in dissociated fetal hepatocytes in culture. Differential expression of metabolic genes were found between fetal and adult livers, suggesting that metabolic features affected clock amplitude. Genome-wide differences in DNA methylation were also found between adult and fetal livers. Some of those epigenetic changes were likely critical for the developmental changes in clock amplitudes. All in all, the unique epigenetic environment and this determined transcripts of the fetal liver determined its internal circadian clock operating on a specific status.