5. The tick-tock of the molecular clock

2017 ◽  
pp. 62-80
Author(s):  
Russell G. Foster ◽  
Leon Kreitzman
Keyword(s):  
Drosophila Melanogaster ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Protein Degradation ◽  
Molecular Clock ◽  
Protein Complex ◽  
Fruit Fly ◽  
Circadian Clocks ◽  
Tissue Specific ◽  
Transcriptional Inhibition

Circadian clocks in animals and plants arise from multiple and interconnected transcription–translation feedback loops that ensure the proper oscillation of thousands of genes in a tissue-specific manner. ‘The tick-tock of the molecular clock’ explains the transcription–translation feedback loop by describing the studies of circadian rhythms in Drosophila melanogaster, the fruit fly. The generation of a robust circadian rhythm entrained by the environment is achieved via multiple elements including the rate of transcription, translation, protein complex assembly, phosphorylation, other post-translation modification events, movement into the nucleus, transcriptional inhibition, and protein degradation. Similar mechanisms have been found in mammals, and insight is provided regarding research into how the mammalian molecular clock is entrained by light.

scholarly journals Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice

Blood ◽  
2017 ◽  
Vol 130 (18) ◽  
pp. 1995-2005 ◽  
Author(s):  
Yue Zhao ◽  
Min Liu ◽  
Xue Ying Chan ◽  
Sue Yee Tan ◽  
Sharrada Subramaniam ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Clock ◽  
Humanized Mice ◽  
Human Leukocytes ◽  
Clock Network ◽  
Key Points ◽  
Human And Mouse

Key Points Human circulating leukocytes in humanized mice reproduce similar circadian oscillations as seen in humans. A novel molecular clock network exhibiting opposite effects on regulating human and mouse leukocyte circadian rhythm is discovered.

scholarly journals Peripheral Sensory Organs Contribute to Temperature Synchronization of the Circadian Clock in Drosophila melanogaster

2021 ◽  
Vol 12 ◽  
Author(s):  
Rebekah George ◽  
Ralf Stanewsky
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Circadian Clock ◽  
Temperature Fluctuations ◽  
Fruit Fly ◽  
Circadian Clocks ◽  
Sensory Cells ◽  
Clock Gene Expression ◽  
External Time ◽  
Peripheral Sensory

Circadian clocks are cell-autonomous endogenous oscillators, generated and maintained by self-sustained 24-h rhythms of clock gene expression. In the fruit fly Drosophila melanogaster, these daily rhythms of gene expression regulate the activity of approximately 150 clock neurons in the fly brain, which are responsible for driving the daily rest/activity cycles of these insects. Despite their endogenous character, circadian clocks communicate with the environment in order to synchronize their self-sustained molecular oscillations and neuronal activity rhythms (internal time) with the daily changes of light and temperature dictated by the Earth’s rotation around its axis (external time). Light and temperature changes are reliable time cues (Zeitgeber) used by many organisms to synchronize their circadian clock to the external time. In Drosophila, both light and temperature fluctuations robustly synchronize the circadian clock in the absence of the other Zeitgeber. The complex mechanisms for synchronization to the daily light–dark cycles are understood with impressive detail. In contrast, our knowledge about how the daily temperature fluctuations synchronize the fly clock is rather limited. Whereas light synchronization relies on peripheral and clock-cell autonomous photoreceptors, temperature input to the clock appears to rely mainly on sensory cells located in the peripheral nervous system of the fly. Recent studies suggest that sensory structures located in body and head appendages are able to detect temperature fluctuations and to signal this information to the brain clock. This review will summarize these studies and their implications about the mechanisms underlying temperature synchronization.

scholarly journals Entrainment of the Drosophila clock by the visual system

2020 ◽  
Vol 15 ◽  
pp. 263310552090370
Author(s):  
Matthias Schlichting
Keyword(s):  
Drosophila Melanogaster ◽  
Visual System ◽  
Clock Synchronization ◽  
Fruit Fly ◽  
Circadian Clocks ◽  
Cyclic Change ◽  
Animal Physiology ◽  
Light Entrainment ◽  
Physiological Evidence ◽  
External Cues

Circadian clocks evolved as an adaptation to the cyclic change of day and night. To precisely adapt to this environment, the endogenous period has to be adjusted every day to exactly 24 hours by a process called entrainment. Organisms can use several external cues, called zeitgebers, to adapt. These include changes in temperature, humidity, or light. The latter is the most powerful signal to synchronize the clock in animals. Research shows that a complex visual system and circadian photoreceptors work together to adjust animal physiology to the outside world. This review will focus on the importance of the visual system for clock synchronization in the fruit fly Drosophila melanogaster. It will cover behavioral and physiological evidence that supports the importance of the visual system in light entrainment.

scholarly journals New Insights Into Cancer Chronotherapies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingxuan Zhou ◽  
Jiechen Wang ◽  
Xiaozhao Zhang ◽  
Qingming Tang
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Clock Genes ◽  
Biological Activities ◽  
Circadian Clocks ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Circadian Clock Genes ◽  
Specific Association ◽  
Mild Toxicity

Circadian clocks participate in the coordination of various metabolic and biological activities to maintain homeostasis. Disturbances in the circadian rhythm and cancers are closely related. Circadian clock genes are differentially expressed in many tumors, and accelerate the development and progression of tumors. In addition, tumor tissues exert varying biological activities compared to normal tissues due to resetting of altered rhythms. Thus, chronotherapeutics used for cancer treatment should exploit the timing of circadian rhythms to achieve higher efficacy and mild toxicity. Due to interpatient differences in circadian functions, our findings advocate an individualized precision approach to chronotherapy. Herein, we review the specific association between circadian clocks and cancers. In addition, we focus on chronotherapies in cancers and personalized biomarkers for the development of precision chronotherapy. The understanding of circadian clocks in cancer will provide a rationale for more effective clinical treatment of tumors.

scholarly journals Circadian rhythms affect bone reconstruction by regulating bone energy metabolism

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Beibei Luo ◽  
Xin Zhou ◽  
Qingming Tang ◽  
Ying Yin ◽  
Guangxia Feng ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Energy Metabolism ◽  
Circadian Rhythms ◽  
Clock Genes ◽  
Therapeutic Potential ◽  
Bone Development ◽  
Feeding Time ◽  
Bone Reconstruction ◽  
Immune Functions ◽  
Tissue Specific

AbstractMetabolism is one of the most complex cellular biochemical reactions, providing energy and substances for basic activities such as cell growth and proliferation. Early studies have shown that glucose is an important nutrient in osteoblasts. In addition, amino acid metabolism and fat metabolism also play important roles in bone reconstruction. Mammalian circadian clocks regulate the circadian cycles of various physiological functions. In vertebrates, circadian rhythms are mediated by a set of central clock genes: muscle and brain ARNT like-1 (Bmal1), muscle and brain ARNT like-2 (Bmal2), circadian rhythmic motion output cycle stagnates (Clock), cryptochrome 1 (Cry1), cryptochrome2 (Cry2), period 1 (Per1), period 2 (Per2), period 3 (Per3) and neuronal PAS domain protein 2 (Npas2). Negative feedback loops, controlled at both the transcriptional and posttranslational levels, adjust these clock genes in a diurnal manner. According to the results of studies on circadian transcriptomic studies in several tissues, most rhythmic genes are expressed in a tissue-specific manner and are affected by tissue-specific circadian rhythms. The circadian rhythm regulates several activities, including energy metabolism, feeding time, sleeping, and endocrine and immune functions. It has been reported that the circadian rhythms of mammals are closely related to bone metabolism. In this review, we discuss the regulation of the circadian rhythm/circadian clock gene in osteoblasts/osteoclasts and the energy metabolism of bone, and the relationship between circadian rhythm, bone remodeling, and energy metabolism. We also discuss the therapeutic potential of regulating circadian rhythms or changing energy metabolism on bone development/bone regeneration.

scholarly journals Running on time: the role of circadian clocks in the musculoskeletal system

2014 ◽  
Vol 463 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Michal Dudek ◽  
Qing-Jun Meng
Keyword(s):  
Circadian Rhythms ◽  
Musculoskeletal System ◽  
Sports Medicine ◽  
Target Genes ◽  
Gene Expression Pattern ◽  
Local Environment ◽  
Global Gene Expression ◽  
Circadian Clocks ◽  
Molecular Clocks ◽  
Tissue Specific

The night and day cycle governs the circadian (24 hourly) rhythm of activity and rest in animals and humans. This is reflected in daily changes of the global gene expression pattern and metabolism, but also in the local physiology of various tissues. A central clock in the brain co-ordinates the rhythmic locomotion behaviour, as well as synchronizing various local oscillators, such as those found in the musculoskeletal system. It has become increasingly recognized that the internal molecular clocks in cells allow a tissue to anticipate the rhythmic changes in their local environment and the specific demands of that tissue. Consequently, the majority of the rhythmic clock controlled genes and pathways are tissue specific. The concept of the tissue-specific function of circadian clocks is further supported by the diverse musculoskeletal phenotypes in mice with deletions or mutations of various core clock components, ranging from increased bone mass, dwarfism, arthropathy, reduced muscle strength and tendon calcification. The present review summarizes the current understanding of the circadian clocks in muscle, bone, cartilage and tendon tissues, with particular focus on the evidence of circadian rhythms in tissue physiology, their entrainment mechanisms and disease links, and the tissue-specific clock target genes/pathways. Research in this area holds strong potential to advance our understanding of how circadian rhythms control the health and disease of the musculoskeletal tissues, which has major implications in diseases associated with advancing age. It could also have potential implications in sports performance and sports medicine.

scholarly journals Circadian rhythm and neurodegenerative disorders

2020 ◽  
Vol 6 (2) ◽  
pp. 71-80
Author(s):  
Michelle Werdann ◽  
Yong Zhang
Keyword(s):  
Circadian Rhythm ◽  
Early Intervention ◽  
Circadian Rhythms ◽  
Neurodegenerative Diseases ◽  
Circadian Clock ◽  
Neurodegenerative Disorders ◽  
Circadian Clocks ◽  
Daily Rhythms ◽  
Animal Physiology ◽  
And Behavior

The circadian clock controls daily rhythms in animal physiology, metabolism, and behavior, such as the sleep‐wake cycle. Disruption of circadian rhythms has been revealed in many diseases including neurodegenerative disorders. Interestingly, patients with many neurodegenerative diseases often show problems with circadian clocks even years before other symptoms develop. Here we review the recent studies identifying the association between circadian rhythms and several major neurodegenerative disorders. Early intervention of circadian rhythms may benefit the treatment of neurodegeneration.

scholarly journals Melatonin, Clock Genes, and Mammalian Reproduction: What Is the Link?

2021 ◽  
Vol 22 (24) ◽  
pp. 13240
Author(s):  
Amnon Brzezinski ◽  
Seema Rai ◽  
Adyasha Purohit ◽  
Seithikurippu R. Pandi-Perumal
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Clock ◽  
Reproductive Performance ◽  
Clock Genes ◽  
Current Knowledge ◽  
Reproductive Function ◽  
The Body ◽  
Molecular Clocks ◽  
Biological Regulation

Physiological processes and behaviors in many mammals are rhythmic. Recently there has been increasing interest in the role of circadian rhythmicity in the control of reproductive function. The circadian rhythm of the pineal hormone melatonin plays a role in synchronizing the reproductive responses of animals to environmental light conditions. There is some evidence that melatonin may have a role in the biological regulation of circadian rhythms and reproduction in humans. Moreover, circadian rhythms and clock genes appear to be involved in optimal reproductive performance. These rhythms are controlled by an endogenous molecular clock within the suprachiasmatic nucleus (SCN) in the hypothalamus, which is entrained by the light/dark cycle. The SCN synchronizes multiple subsidiary oscillators (clock genes) existing in various tissues throughout the body. The basis for maintaining the circadian rhythm is a molecular clock consisting of transcriptional/translational feedback loops. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance. This mini review summarizes the current knowledge regarding the interrelationships between melatonin and the endogenous molecular clocks and their involvement in reproductive physiology (e.g., ovulation) and pathophysiology (e.g., polycystic ovarian syndrome).

Organization of endogenous clocks in insects

2005 ◽  
Vol 33 (5) ◽  
pp. 957-961 ◽  
Author(s):  
C. Helfrich-Förster
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Fruit Fly ◽  
Circadian Clocks ◽  
Rhythm Generation ◽  
Similarities And Differences ◽  
The Brain ◽  
Master Clock

Insect and mammalian circadian clocks show striking similarities. They utilize homologous clock genes, generating self-sustained circadian oscillations in distinct master clocks of the brain, which then control rhythmic behaviour. The molecular mechanisms of rhythm generation were first uncovered in the fruit fly Drosophila melanogaster, whereas cockroaches were among the first animals where the brain master clock was localized. Despite many similarities, there exist obvious differences in the organization and functioning of insect master clocks. These similarities and differences are reviewed on a molecular and anatomical level.

scholarly journals Hox dosage contributes to flight appendage morphology in Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel Paul ◽  
Guillaume Giraud ◽  
Katrin Domsch ◽  
Marilyne Duffraisse ◽  
Frédéric Marmigère ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Differential Expression ◽  
Hox Genes ◽  
Expression Profiles ◽  
Fruit Fly ◽  
Insect Species ◽  
Wing Morphology ◽  
Hox Proteins ◽  
Spatial Expression ◽  
Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

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