The ontogeny of circadian clock gene expression during mouse fetal development

The circadian clock in the suprachiasmatic nucleus and peripheral tissues functions to regulate key physiological and cellular systems in a cycle approximating 24 h. Understanding the ontogeny of the circadian clock mechanism during mammalian development is incomplete. Accordingly, we used the mouse as a model and a previously published RNAseq dataset to determine when expression of core genes regulating the circadian clock increase in transcript abundance in fetal and postnatal brain, heart, liver, and kidney. Transcripts for all six core genes examined (Clock, Bmal1, Per1, Per2, Cry1, and Cry2) were identified in all tissues and time points. For brain, there was a small increase in Clock at E13.5 and a larger increase at E18.5. Similarly, Bmal1 transcript abundance increased slightly at E14.5 and to a greater degree at E17.5, Per2 increased slightly at E15.5 and remained constant until after birth and Cry2 increased slightly at E18.5. For liver, transcript abundance of most genes increased at the end of gestation, with increases observed for Clock at E18.5, and for Bmal1, Per2, and Cry2 at E17.5. The genes whose expression increased before birth in heart was Clock (at E18.5), and Per2 (at E15.5) and the genes whose expression increased before birth in kidney were Clock (E18.5), Bmal1 (E15.5) and Per1 (P18.5). For all tissues, there were further increases in transcript abundance for most genes in the postnatal period with the exception of Cry1 (all tissues) and Per1 (liver and kidney). Results support the idea that the organization of the molecular clock is more advanced for the fetal brain and liver than for fetal heart and kidney. Furthermore, based on changes in gene expression, components of the molecular clock continued to mature after birth.