The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated tissues can partition clock function to generate and coordinate different rhythms. In both cases, the temporal coordination of a multi-oscillator system is essential for producing robust circadian rhythms of gene expression and biological activity.

http://www.ifc.unam.mx/curso_ritmos/capitulo8/Bell-Pedersen05.pdf

Circadian rhythms from multiple oscillators: lessons from diverse organisms

Mammals have circadian clocks in peripheral tissues, but there is no direct evidence of their physiological importance. Unlike the suprachiasmatic nucleus clock that is set by light and drives rest–activity and fasting–feeding cycles, peripheral clocks are set by daily feeding, suggesting that at least some contribute metabolic regulation. The liver plays a well known role in glucose homeostasis, and we report here that mice with a liver-specific deletion of Bmal1, an essential clock component, exhibited hypoglycemia restricted to the fasting phase of the daily feeding cycle, exaggerated glucose clearance, and loss of rhythmic expression of hepatic glucose regulatory genes. We conclude that the liver clock is important for buffering circulating glucose in a time-of-day-dependent manner. Our findings suggest that the liver clock contributes to homeostasis by driving a daily rhythm of hepatic glucose export that counterbalances the daily cycle of glucose ingestion resulting from the fasting–feeding cycle.

https://www.pnas.org/content/pnas/105/39/15172.full.pdf

Physiological significance of a peripheral tissue circadian clock

To accommodate daily recurring environmental changes, animals show cyclic variations in behaviour and physiology, which include prominent behavioural states such as sleep-wake cycles but also a host of less conspicuous oscillations in neurological, metabolic, endocrine, cardiovascular and immune functions. Circadian rhythmicity is created endogenously by genetically encoded molecular clocks, whose components cooperate to generate cyclic changes in their own abundance and activity, with a periodicity of about a day. Throughout the body, such molecular clocks convey temporal control to the function of organs and tissues by regulating pertinent downstream programmes. Synchrony between the different circadian oscillators and resonance with the solar day is largely enabled by a neural pacemaker, which is directly responsive to certain environmental cues and able to transmit internal time-of-day representations to the entire body. In this Review, we discuss aspects of the circadian clock in Drosophila melanogaster and mammals, including the components of these molecular oscillators, the function and mechanisms of action of central and peripheral clocks, their synchronization and their relevance to human health.

Molecular mechanisms and physiological importance of circadian rhythms.

http://www.ifc.unam.mx/pages/curso_ritmos/capitulo7/Hardin_2005.pdf

The circadian timekeeping system of Drosophila.

Circadian clocks organize behavior and physiology to adapt to daily environmental cycles. Genetic approaches in the fruit fly, Drosophila melanogaster, have revealed widely conserved molecular gears of these 24-h timers. Yet much less is known about how these cell-autonomous clocks confer temporal information to modulate cellular functions. Here we discuss our current knowledge of circadian clock function in Drosophila, providing an overview of the molecular underpinnings of circadian clocks. We then describe the neural network important for circadian rhythms of locomotor activity, including how these molecular clocks might influence neuronal function. Finally, we address a range of behaviors and physiological systems regulated by circadian clocks, including discussion of specific peripheral oscillators and key molecular effectors where they have been described. These studies reveal a remarkable complexity to circadian pathways in this “simple” model organism.

Circadian Organization of Behavior and Physiology in Drosophila

Circadian clocks in antennal neurons are necessary and sufficient for olfaction rhythms in Drosophila.

https://www.cell.com/current-biology/pdf/S0960-9822(10)00004-7.pdf

Regulation of Gustatory Physiology and Appetitive Behavior by the Drosophila Circadian Clock

https://www.cell.com/current-biology/pdf/S0960-9822(08)00582-4.pdf

Spike Amplitude of Single-Unit Responses in Antennal Sensillae Is Controlled by the Drosophila Circadian Clock

G Protein-Coupled Receptor Kinase 2 Is Required for Rhythmic Olfactory Responses in Drosophila

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Circadian clocks in antennal neurons are necessary and sufficient for olfaction rhythms in Drosophila.

Regulation of Gustatory Physiology and Appetitive Behavior by the Drosophila Circadian Clock

Spike Amplitude of Single-Unit Responses in Antennal Sensillae Is Controlled by the Drosophila Circadian Clock

G Protein-Coupled Receptor Kinase 2 Is Required for Rhythmic Olfactory Responses in Drosophila