Postnatal ontogenesis of the circadian clock within the rat liver
Postnatal ontogenesis of the circadian clock within the rat liver
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DOI：
10.1152/ajpregu.00184.2006
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发表时间：
2007-03-01
影响因子：
2.8
通讯作者：
Sumova, Alena
中科院分区：
文献类型：
--
作者：
Sladek, Martin;Jindrakova, Zuzana;Sumova, Alena
在哺乳动物中，视交叉上核（SCN）内的昼夜节律振荡器在许多周围组织中携带昼夜节律钟。中央时钟和外围时钟共享一个控制日常时间测量的分子核心时钟机制。在大鼠SCN中，分子时钟在出生后的个体发生过程中逐渐发育。本研究的目的是阐明在个体发育过程中，时钟基因在大鼠肝脏中的表达何时开始具有节律性。采用实时实时RT-PCR分析了胚胎20天（E20）胎儿、出生后2岁（P2）幼犬、P10、P20、P30和成人肝脏中时钟基因Per1、Per2、Cry1、clock、Rev-Erb α和Bmal1 mRNA的日表达谱。在E20时，只有Rev-Erb α的高振幅节律和Cry1的低振幅变化，而其他时钟基因的表达没有明显的昼夜节律。在P2时，Rev-Erb α的表达出现了高幅度的节律，Bmal1的表达出现了低幅度的变化，但其他基因的表达没有变化。在P10时，只有Per1和Rev-Erb α的表达存在显著的节律。在P20时，Per1、Per2、Rev-Erb α和Bmal1的表达有明显的昼夜节律，但Cry1和Clock的表达尚未检测到。P30时，所有时钟基因均有节律性表达。节律的阶段在所有被研究的发育阶段之间变化，直到达到成年阶段。数据表明，大鼠肝脏中分子时钟系统的发育是逐步进行的，大约在出生后30天完成。
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.