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Am J Physiol Regul Integr Comp Physiol 292: R1224-R1229, 2007. First published November 9, 2006; doi:10.1152/ajpregu.00184.2006
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Postnatal ontogenesis of the circadian clock within the rat liver

Martin Sládek, Zuzana Jindráková, Zdenka Bendová, and Alena Sumová

Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Submitted 15 March 2006 ; accepted in final form 29 October 2006

In mammals, the circadian oscillator within the suprachiasmatic nuclei (SCN) entrains circadian clocks in numerous peripheral tissues. Central and peripheral clocks share a molecular core clock mechanism governing daily time measurement. In the rat SCN, the molecular clockwork develops gradually during postnatal ontogenesis. The aim of the present work was to elucidate when during ontogenesis the expression of clock genes in the rat liver starts to be rhythmic. Daily profiles of mRNA expression of clock genes Per1, Per2, Cry1, Clock, Rev-Erb{alpha}, and Bmal1 were analyzed in the liver of fetuses at embryonic day 20 (E20) or pups at postnatal age 2 (P2), P10, P20, P30, and in adults by real-time RT-PCR. At E20, only a high-amplitude rhythm in Rev-Erb{alpha} and a low-amplitude variation in Cry1 but no clear circadian rhythms in expression of other clock genes were detectable. At P2, a high-amplitude rhythm in Rev-Erb{alpha} and a low-amplitude variation in Bmal1 but no rhythms in expression of other genes were detected. At P10, significant rhythms only in Per1 and Rev-Erb{alpha} expression were present. At P20, clear circadian rhythms in the expression of Per1, Per2, Rev-Erb{alpha}, and Bmal1, but not yet of Cry1 and Clock, were detected. At P30, all clock genes were expressed rhythmically. The phase of the rhythms shifted between all studied developmental periods until the adult stage was achieved. The data indicate that the development of the molecular clockwork in the rat liver proceeds gradually and is roughly completed by 30 days after birth.

circadian rhythms; clock genes; development; peripheral clock; rat



Address for reprint requests and other correspondence: A. Sumová, Institute of Physiology, Vídenská 1083, Praha 4, 142 20, Czech Republic (e-mail: sumova{at}biomed.cas.cz)




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