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At least 1,099 records · Page 61Linked to original sources
PubMed2001

Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.

The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes.

Animals↗
PubMed2001

The circadian gene Clock is restricted to the anterior neural plate early in development and is regulated by the neural inducer noggin and the transcription factor Otx2.

The circadian cycle is a simple, universal molecular mechanism for imposing cyclical control on cellular processes. Here we have examined the regulation of one of the key circadian genes, Clock, in early Xenopus development. We find that the expression of Clock is dependent on developmental stage, not on time per se, and is mostly restricted to the anterior neural plate. It's expression can be induced by the secreted polypeptide noggin, and subsequently upregulated by Otx2, a transcription factor required for the determination of anterior fate.

Animals↗
PubMed2002

From head to tail: links between the segmentation clock and antero-posterior patterning of the embryo.

Periodic production of somites along the anteroposterior axis of the vertebrate body involves a molecular oscillator, the 'segmentation clock', which can be visualized through the periodic activation of genes linked to the Notch pathway. Recent findings show that oscillations initiate at gastrula stages and point to a role for FGF signaling in positioning the segmental boundaries. This clock also controls aspects of spatio-temporal Hox gene activation thus ensuring a perfect match between segment boundary position and future regional identity of the somites.

Animals↗
PubMed2003

Oscillations, clocks and segmentation.

Notch signalling molecules, such as the basic helix-loop-helix factors Hes1 and Hes7, periodically change their expression in the presomitic mesoderm, and each cycle of gene expression is associated with somite formation (every two hours in mouse). This cyclic expression is the manifestation of an intrinsic mechanism, called the segmentation clock, which is essential for coordinated somite segmentation. Interestingly, the oscillatory expression of Hes1 is observed in many cell types after serum stimulation, suggesting that this ultradian clock is not unique to presomitic mesoderm cells but widely distributed. This oscillation depends on the negative feedback loop, and once its promoter is constitutively activated, Hes1 seems to start oscillatory gene expression autonomously. Thus, Hes1 acts as a device that transduces a direct current of input into an alternating current, which ticks the hours in many biological systems.

Animals↗
PubMed1998

Functional and evolutionary implications of natural variation in clock genes.

Nearly all studies of natural variation within clock genes involve the period (per) locus, which was originally isolated in the fruit-fly. Intra- and interspecific work on per has focused mostly on a region of Thr-Gly or Ser-Gly repeats, which show rapid length and sequence evolution. The functional implications of nucleotide variation in this repetitive array have been characterised using behavioural, molecular, ecological, structural and statistical analyses. A population genetics approach to variation in per has also been useful in defining species histories within Drosophilids and, in some cases, in implicating selective processes in the evolution of the per gene. Interspecific analysis of per expression patterns reveals evolutionary alterations in this clock gene's regulation.

Animals↗
PubMed2001

Circadian rhythms: mop up the clock!

All circadian clock genes discovered in Drosophila have mammalian counterparts with extensive sequence homology. Similarities and differences have been identified between insect and mammalian oscillators. Recent studies have shed new light on two mammalian clock components: Mop3 and Per2.

ARNTL Transcription Factors↗
PubMed2001

Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY.

BACKGROUND: The biological clock synchronizes the organism with the environment, responding to changes in light and temperature. Drosophila CRYPTOCHROME (CRY), a putative circadian photoreceptor, has previously been reported to interact with the clock protein TIMELESS (TIM) in a light-dependent manner. Although TIM dimerizes with PERIOD (PER), no association between CRY and PER has previously been revealed, and aspects of the light dependence of the TIM/CRY interaction are still unclear. RESULTS: Behavioral analysis of double mutants of per and cry suggested a genetic interaction between the two loci. To investigate whether this was reflected in a physical interaction, we employed a yeast-two-hybrid system that revealed a dimerization between PER and CRY. This was further supported by a coimmunoprecipitation assay in tissue culture cells. We also show that the light-dependent nuclear interactions of PER and TIM with CRY require the C terminus of CRY and may involve a trans-acting repressor. CONCLUSIONS: This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediating light responses. A model for the light dependence of CRY is discussed.

Animals↗
PubMed1998

Vertebrate segmentation: the clock is linked to Notch signalling.

The periodic formation of somites during vertebrate segmentation has been suggested to involve a molecular 'segmentation clock'. Recent observations of cyclic Lunatic fringe expression in chick and mouse embryos link the segmentation clock to Delta-Notch signalling.

Animals↗
PubMed2000

Microbial circadian oscillatory systems in Neurospora and Synechococcus: models for cellular clocks.

Common regulatory patterns have emerged among the feedback loops lying within circadian systems. Significant progress in dissecting the mechanism of clock resetting by temperature and the role of the WC proteins in the Neurospora light response has accompanied documentation of the importance of nuclear localization and phosphorylation-induced turnover of FRQ to this circadian cycle. The long-awaited molecular description of a transcription/translation loop in the Synechococcus circadian system represents a quantal step forward, followed by the identification of additional important proteins and interactions. Finally, the adaptive significance of rhythms in Synechococcus and by extension in all clocks nicely ties up an extraordinary year.

Biological Clocks↗
PubMed1998

The cyanobacterial circadian system: a clock apart.

Several new molecular components of the circadian clocks of animals, fungi, and bacteria have been unveiled in the past two years. Enough parts are now identified to indicate that there is more than one way to build a biological clock, although there are parallels in the cycling molecular events among disparate groups of organisms.

Animals↗
PubMed1998

Time at the end of the millennium: the Neurospora clock.

In the past two years we have entered the log phase for unraveling the molecular clockworks. Rapid progress in understanding the Neurospora clock has been complemented by a flood of information from diverse systems including cyanobacteria, insects and mice. There are broadly conserved features in transcription/translation based feedback loops. Conservation is also found at the sequence level, from fungi to mammals, in the PAS domains of the heterodimeric partners of the transcription factors that act as the positive components of the feedback cycle. Pivotal PAS proteins from Neurospora, the WCs, provide an evolutionary link connecting the clock in insects and mammals to the fungi and to light-harvesting proteins from bacteria.

Animals↗
PubMed2002

Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis.

Somitogenesis requires a segmentation clock and Notch signaling. Lunatic fringe (Lfng) expression in the presomitic mesoderm (PSM) cycles in the posterior PSM, is refined in the segmenting somite to the rostral compartment, and is required for segmentation. We identify distinct cis-acting regulatory elements for each aspect of Lfng expression. Fringe clock element 1 (FCE1) represents a conserved 110 bp region that is necessary to direct cyclic Lfng RNA expression in the posterior PSM. Mutational analysis of E boxes within FCE1 indicates a potential interplay of positive and negative transcriptional regulation by cyclically expressed bHLH proteins. A separable Lfng regulatory region directs expression to the prospective rostral aspect of the condensing somite. These independent Lfng regulatory cassettes advance a molecular framework for deciphering somite segmentation.

5' Flanking Region↗
PubMed1999

Conditioned stimulus control in the rat circadian system depends on clock resetting during conditioning.

The authors examined the ability of a conditioned stimulus (CS; mild air disturbance) previously paired with an entraining light pulse to reset the circadian pacemaker in rats. Rats were entrained to a single 30-min light stimulus delivered every 25 hr or 24 hr (T cycle). Each daily light presentation was paired with the CS. After at least 20 days of stable entrainment to each of the T cycles, the rats were allowed to free run and were then presented with the CS at circadian time 15. CS-induced phase shifts in wheel-running activity rhythms were taken as evidence for conditioning. For the most part, conditioning occurred after CS-light pairings on the 25-hr but not 24-hr T cycle. The results suggest that CS control of the circadian clock phase depends on the effect that the entraining light pulse has on the clock during conditioning.

Animals↗
PubMed2004

Differential modulation of clock speed by the administration of intermittent versus continuous cocaine.

The roles that psychostimulant sensitization and tolerance play in temporal perception in the seconds-to-minutes range were assessed in rats. Cocaine (20 mg/kg/day) was administered for 2 weeks either intermittently via daily injections (induces sensitization) or continuously via an osmotic minipump (induces tolerance). Interval timing was evaluated throughout administration and withdrawal. Injections of cocaine caused immediate, proportional, leftward shifts in peak times, indicating an increase in the speed of an internal clock. These shifts grew progressively larger with repeated administration, indicating that stimulant-induced increases in clock speed can be sensitized. Continuous cocaine administration produced no reliable effects. These results suggest that the mechanisms of sensitization may play a considerable role in drug-induced alterations of the perception of time.

Animals↗
PubMed1999

Assignment of circadian function for the Neurospora clock gene frequency.

Circadian clocks consist of three elements: entrainment pathways (inputs), the mechanism generating the rhythmicity (oscillator), and the output pathways that control the circadian rhythms. It is difficult to assign molecular clock components to any one of these elements. Experiments show that inputs can be circadianly regulated and outputs can feed back on the oscillator. Mathematical simulations indicate that under- or overexpression of a gene product can result in arrhythmicity, whether the protein is part of the oscillator or substantially part of a rhythmically expressed input pathway. To distinguish between these two possibilities, we used traditional circadian entrainment protocols on a genetic model system, Neurospora crassa.

Biological Clocks↗
PubMedDate not supplied

An endogenous annual clock in the toxic marine dinoflagellate Gonyaulax tamarensis.

Blooms of the toxic dinoflagellate Gonyaulax tamarensis (synonyms Protogonyaulax tamarensis and Alexandrium tamarense) cause outbreaks of paralytic shellfish poisoning (PSP) in coastal waters throughout the world. In the Gulf of Maine, episodes occur between April and November, a seasonality due in part to life-cycle alternations between motile, vegetative cells and resting cysts which overwinter in bottom sediments. Newly formed cysts have a mandatory 2-6 month dormancy period during which germination is not possible, but once mature, the resting state will continue if temperatures are unfavourable or oxygen is unavailable. We now report another factor controlling germination of cysts of G. tamarensis from deep coastal waters--an endogenous annual clock that can override an otherwise favourable environment for germination. Similar annual variability in germination has not been observed for cysts of this species from shallow estuaries. These results represent the first conclusive demonstration of an endogenous circannual rhythm in a marine plant. They are evolutionarily and ecologically significant because an endogenous annual clock can lead to the release of motile cells into deep and relatively invariant bottom waters at those times when temperature and light at the surface are suitable for growth. In shallow waters where seasonal variability is large and extends to bottom sediments, a strategy similar to that of the seeds of terrestrial plants would be more appropriate, namely a direct coupling between germination and the external environment.

Biological Clocks↗
PubMedDate not supplied

A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene.

Complementary DNA cloning of the transcripts of the Drosophila clock gene period reveals three distinct transcripts. These result from unusual splicing pathways, one involving a CG 3' splice site and one resulting in the use of two different reading frames in one exon, and they predict three separate proteins. Two of the cloned cDNAs can restore clock function to mutant arrhythmic flies.

Animals↗
PubMedDate not supplied

A role for casein kinase 2alpha in the Drosophila circadian clock.

Circadian clocks drive rhythmic behaviour in animals and are regulated by transcriptional feedback loops. For example, the Drosophila proteins Clock (Clk) and Cycle (Cyc) activate transcription of period (per) and timeless (tim). Per and Tim then associate, translocate to the nucleus, and repress the activity of Clk and Cyc. However, post-translational modifications are also critical to proper timing. Per and Tim undergo rhythmic changes in phosphorylation, and evidence supports roles for two kinases in this process: Doubletime (Dbt) phosphorylates Per, whereas Shaggy (Sgg) phosphorylates Tim. Yet Sgg and Dbt often require a phosphoserine in their target site, and analysis of Per phosphorylation in dbt mutants suggests a role for other kinases. Here we show that the catalytic subunit of Drosophila casein kinase 2 (CK2alpha) is expressed predominantly in the cytoplasm of key circadian pacemaker neurons. CK2alpha mutant flies show lengthened circadian period, decreased CK2 activity, and delayed nuclear entry of Per. These effects are probably direct, as CK2alpha specifically phosphorylates Per in vitro. We propose that CK2 is an evolutionary link between the divergent circadian systems of animals, plants and fungi.

Active Transport, Cell Nucleus↗