叙利亚仓鼠生物钟基因的发育表达

Xiaodong Li , Fred C. Davis
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引用次数: 37

摘要

由多个时钟基因组成的转录/翻译反馈回路被认为是细胞、组织和有机体水平上昼夜节律振荡的必要条件。我们检测了三个时钟基因(Bmal1, Cry1和Per1)在叙利亚仓鼠的发育表达,以探测视交叉上核(SCN)神经发生完成后的头4天内的振荡特性。在恒定昏暗的光线下,每天在大坝的昼夜节律时间6,12和18采集样本,持续4天,并使用35s标记的RNA探针进行原位杂交。收集时间基于成人SCN中Bmal1和Per1节律的阶段,以及在出生后第2天CT6和18时观察到的Per1 mRNA的差异。在发育研究中,每个大脑的切片都被并行处理以获得这三种基因。Bmal1在胎儿SCN中显著表达,而Per1和Cry1仅弱表达。这三个基因的转录本在出生后显示出更高的丰度。在随后的年龄,Bmal1表现出显著的下降,而Per1继续高于产前水平。Cry1基因在不同昼夜时间存在显著差异,而Per1和Bmal1基因没有昼夜变化。在胎儿SCN中,尽管有证据表明当时存在可携带的起搏器,但在成人中观察到的分子振荡并不存在。在早期SCN发育过程中缺乏强大的振荡可能部分解释了药物对胎儿/新生儿时钟的强相位设置效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Developmental expression of clock genes in the Syrian hamster

Transcription/translation feedback loops consisting of multiple clock genes are thought to be essential for circadian oscillations at cellular, tissue and organismal levels. We examined the developmental expressions of three clock genes (Bmal1, Cry1 and Per1) in the Syrian hamster to probe the oscillatory properties of the suprachiasmatic nucleus (SCN) over the first 4 days after the completion of SCN neurogenesis. Samples were taken at the dam's circadian times 6, 12, and 18 daily over 4 days in constant dim light and processed for in situ hybridization using 35S-labeled RNA probes. Collection times were based on the phases of Bmal1 and Per1 rhythms in adult SCN and on an observed difference in Per1 mRNA at CT6 and 18 on postnatal day 2. For the developmental study, sections from each brain were processed in parallel for the three genes. Bmal1 was prominently expressed in the fetal SCN while Per1 and Cry1 were only weakly expressed. Transcripts of all three genes showed higher abundance just after birth. At subsequent ages, Bmal1 showed a significant decrease, while Per1 continued to be greater than prenatal levels. Significant variation was detected across circadian times for Cry1, but no circadian variation was detected for Per1 and Bmal1. Molecular oscillations equivalent to those observed in adults were not present in the fetal SCN despite evidence for an entrainable pacemaker at that time. An absence of robust oscillations during early SCN development may in part explain the strong phase-setting effects of pharmacological agents on the fetal/neonatal clock.

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