Genetics of Circadian Rhythms in Mammalian Model Organisms

Sep 20, 2011Advances in genetics

Genetic factors controlling daily biological rhythms in mammals

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Abstract

The mammalian circadian system involves a central pacemaker in the hypothalamus that coordinates daily rhythms in behavior.

The central pacemaker is influenced by the environmental light/dark cycle.
Molecular oscillations in gene expression are driven by interconnected feedback loops of transcription and translation.
Single-gene mutations challenge the resilience of the circadian system but do not disrupt its function.
Accessory transcriptional loops enhance the stability of circadian oscillations.
Epigenetic mechanisms play a role in regulating circadian gene expression.
Interactions among central and peripheral oscillators contribute to the emergence of daily behavioral rhythms.

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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.

Genetics of Circadian Rhythms in Mammalian Model Organisms

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