Genetics of circadian rhythms in Mammalian model organisms.
Genetics of circadian rhythms in Mammalian model organisms.
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DOI：
10.1016/b978-0-12-387690-4.00006-4
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发表时间：
2011
影响因子：
--
通讯作者：
Takahashi, Joseph S.
中科院分区：
文献类型：
--
作者：
Lowrey, Phillip L.;Takahashi, Joseph S.
哺乳动物的昼夜节律系统是一个复杂的分层时间网络，它是围绕着一个独特的耦合细胞的合奏，包括在下丘脑的视交叉上核的主要昼夜节律起搏器。这个中央起搏器每天都受到环境光/暗周期的影响，并将同步信号传输到全身组织中的细胞自主振荡器。在中枢起搏器和外周组织的细胞内，基因表达振荡发生的潜在分子机制涉及转录和翻译的相互关联的反馈回路。在过去的10年里，我们已经了解了很多关于这个系统的遗传学，包括当受到单基因突变的挑战时，它是如何特别有弹性的，辅助转录环如何增强振荡的鲁棒性，表观遗传机制如何有助于控制昼夜节律基因表达，以及如何从耦合的神经元网络中产生紧急时钟特性。在这里，我们将探索哺乳动物昼夜节律系统的遗传学，从细胞自主分子振荡，中央和外周振荡器之间的相互作用，并最终在动物中观察到的日常行为节奏。
The mammalian circadian system is a complex hierarchical temporal network which is organized around an ensemble of uniquely coupled cells comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. This central pacemaker is entrained each day by the environmental light/dark cycle and transmits synchronizing cues to cell-autonomous oscillators in tissues throughout the body. Within cells of the central pacemaker and the peripheral tissues, the underlying molecular mechanism by which oscillations in gene expression occur involves interconnected feedback loops of transcription and translation. Over the past 10 years we have learned much regarding the genetics of this system, including how it is particularly resilient when challenged by single-gene mutations, how accessory transcriptional loops enhance the robustness of oscillations, how epigenetic mechanisms contribute to the control of circadian gene expression, and how, from coupled neuronal networks, emergent clock properties arise. Here we will explore the genetics of the mammalian circadian system from cell-autonomous molecular oscillations, to interactions among central and peripheral oscillators and ultimately, to the daily rhythms of behavior observed in the animal.