Pigment dispersing factor

Last updated
Pigment dispersing factor (pdf)
Identifiers
Organism D. melanogaster
SymbolPdf
Entrez 43193
RefSeq (mRNA) NM_079793
RefSeq (Prot) NP_524517
UniProt O96690
Other data
Chromosome 3R: 22.28 - 22.28 Mb
Search for
Structures Swiss-model
Domains InterPro
Pigment-dispersing hormone
Identifiers
SymbolPigment_DH
Pfam PF06324
InterPro IPR009396
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Pigment dispersing factor (pdf) is a gene that encodes the protein PDF, which is part of a large family of neuropeptides. [1] Its hormonal product, pigment dispersing hormone (PDH), was named for the diurnal pigment movement effect it has in crustacean retinal cells upon its initial discovery in the central nervous system of arthropods. [1] The movement and aggregation of pigments in retina cells and extra-retinal cells is hypothesized to be under a split hormonal control mechanism. [1] One hormonal set is responsible for concentrating chromatophoral pigment by responding to changes in the organism's exposure time to darkness. Another hormonal set is responsible for dispersion and responds to the light cycle. [1] However, insect pdf genes do not function in such pigment migration since they lack the chromatophore. [2]

Contents

The gene was first isolated and studied in Drosophila by Jeffrey C. Hall's laboratory at Brandeis University in 1998, and has been found to function as a neuromodulator and coupling factor in controlling circadian rhythms. [3] [4] A neuromodulator is a neuroregulator that can act on other neurons in close proximity or far away, altering the effect of neurotransmitters without itself initiating depolarization. [5]

Discovery

Pigment dispersing factor (pdf) was first discovered in the central nervous system of arthropods by K. Ranga Rao and John P. Riehm in 1993. They noted color changes caused by intracellular pigment movements and hypothesized that crustacean color change is caused by the dispersion of retinal chromatophore pigments. [1] However, Hall's lab was the first to isolate and study the gene itself.

Also contributing to the discovery of pdf was German scientist Charlotte Helfrich-Forster. In 2000, she studied pdf involvement with behavioral rhythms in Drosophila. Helfrich-Forster discovered that misexpressing pdf in neurons with dorsal and central brain axon terminals affected activity rhythms. From this she concluded that pdf is a neuromodulator in the dorsal and central brain that acts upon behavioral rhythms. [4]

Perhaps the most influential contributor to the discovery and analysis of pdf and its role in circadian systems was Paul H. Taghert. The laboratories of Paul H. Taghert, Jeff Hall, and Michael Rosbash identified a null allele of the pdf gene. In addition, they utilized the GAL4/UAS system to knock out first pdf and then the entire pdf neuron. They found that the pdf and pdf neuron knockouts resulted in the destruction of some behavioral rhythms, but not all of them. They thus concluded that PDF is likely a circadian clock output. [6]

Recently, the Taghert lab reported that each of the five major pacemaker groups in the fly brain exhibits a daily large calcium transient. The transients are distributed across the 24 hr day such that the PDF-expressing s-LNv (small lateral neuron) peak around dawn and the LNd (which are implicated in control of the evening locomotor behavior) peak in the late day. Other pacemaker groups peak at mid-day or mid-night phases. In the absence of PDF signaling, all pacemakers still exhibit a daily calcium transient, but two groups are anomalously phase-shifted to peak in the morning, synchronous with the s-LNv. These observations indicate PDF signaling is required to produce large (many-hour) phase differences to ensure a normal sequence of temporal outputs in the circadian neural circuit. [7]

Gene characteristics

In Drosophila, the pdf gene is intronless and is located at 97B on the third chromosome. [6] It exists in a single copy per haploid genome and the approximately 0.8 kb transcript is expressed in the Drosophila's head. [8] The cDNA clone in flies has 1080 base pairs with a single exon. [2] Six alleles of this gene have been reported and are found in dorsal lateral neurons and the ventral lateral neurons in the Drosophila brain and also in some abdominal ganglion neurons. [9]

Role in the circadian pathways

In the Drosophila brain, a group of cells called the lateral ventral neurons is thought to be a subset of the principal pacemaker regulating the circadian rhythm of Drosophila locomotion. [10] Release of PDF, which is expressed by some of these specialized cells, is believed to be a primary output of oscillations within these cells, and it serves to coordinate and couple the morning and evening phases of fly behavior. [10]

E and M cells

The 150 pacemaker neurons in Drosophila are organized into two groups of cells called M (morning) and E (evening) oscillators in the ventral and dorsal lateral neurons (LNs). [11] These two groups of cells were first observed by Colin Pittendrigh in 1976. As indicated by their names, the two oscillators control circadian rhythm at different times of the day, yet the two must coordinate to synchronize circadian activity.

PDF is found in cells of the M oscillators and regulates the anticipatory activity of flies prior to light exposure. This anticipatory activity indicates that the flies are entrained to the light-dark schedule. [10] PDF synchronizes phase of M oscillators, while in E oscillators PDF delays their cycling and increases their amplitude. [10] This PDF-induced delay causes evening behaviors to peak after morning behaviors, causing an antiphasic rhythm. Stoleru et al. used mosaic transgenic animals with different circadian periods to study the two oscillators. Their study showed that M-cells periodically send a "reset" signal which determines the oscillations of the E-cells. It is believed that the reset signal is PDF, because it is M-cell specific and plays a large role in maintaining normal rhythmicity. [12]

Morning behaviors are controlled by a subset of LN’s called lateral ventral neurons (LNv). These neurons express PDF. Meanwhile, evening behaviors are controlled by a subset called lateral dorsal neurons (LNd), which do not express PDF. [13] PDF from small lateral ventral neurons (s-LNv) is responsible for the maintenance of a free-running rhythm, while PDF from large lateral ventral neurons is not required for normal behavior. [14] Experiments at Brandeis University have shown that PDF neuropeptide is localized in s-LNv that specifically control morning anticipatory behavior. [15] However, it has been found that large LNv working with other circadian neurons is sufficient to rescue the morning anticipation behavior and startle response in s-LNv-ablated flies. [16] Thus, PDF's role in setting the free-running rhythm and the timing of light-dark cycles comes from both types of lateral ventral neurons.

Further evidence of distinct E and M peaks in Drosophila was provided by Grima et al. [17] This work confirmed that the small lateral ventral neurons, which express PDF, are necessary for the morning peak in Drosophila circadian rhythms. [17] Flies lacking functional s-LNv did not possess a lights-on anticipatory activity for the morning peak. [17] The evening bout of activity was advanced, demonstrating the necessity of s-LNv neurons to both establish morning rhythms and couple these rhythms to the evening activity rhythms. [17]

Other behavioral aspects of Drosophila such as eclosion activity have been monitored with ectopic expression of pdf, which in this case is concentrated in the dorsal central brain. [4] These alterations in expression caused severely altered rhythmic behavior in eclosion of larvae, further substantiating the evidence that PDF modulates the rhythmic control of Drosophila behavior. [4]

The PDF receptor

The PDF receptor is necessary for rhythmicity since it acts as a binding site for PDF on the pacemaker or 'clock' neurons. The PDF receptor, along with the receptor of its mammalian homolog, vasoactive intestinal peptide (VIP), is known to be a G-protein-coupled receptor of the B1 subfamily. Flies with mutant PDF receptors are arrhythmic or show weak short-period behavioral rhythms. [18]

In a 12:12 light-dark cycle, normal flies exhibited locomotor behavior with a morning peak around dawn and an evening peak around dusk. Loss of PDF or loss of PDF-secreting LNvs resulted in weak or no morning peak, and an approximately 2-hour advance in the evening peak in a light-dark cycle. In constant conditions, loss of the PDF receptor or PDF secreting-cells resulted in desynchrony among the clock neurons. [11]

Seol Hee Im and Paul H. Taghert used pdfr mutant flies (pdfr3369 and pdfr5304) to engineer pdfr-GAL4 lines to show that Gal4 mediated rescue of pdfr phenotypes is insufficient to provide complete behavioral rescue. A series of GAL4 driver experiments found that any rescue experiments using Gal4-UAS system always produced incomplete rescue. Unlike pdfr-GAL4 lines however, the 70-kB pdfr-myc transgene is capable of fully rescuing the circadian behavioral deficiencies of the pdfr mutant flies. Thus, a 70 kN PDF receptor transgene leads to complete rescue of the circadian behavioral deficiencies of the pdfr mutant flies. This transgene is widely expressed among pacemakers and also found in a limited number of non pacemaker cells. [11] [15]

Circadian output

In a series of experiments done at Washington University School of Medicine and Brandeis University, pdf was shown to be critical for circadian output coordination. [10] Flies mutant at the pdf gene locus displayed arrhythmic circadian oscillation. Wild type flies, over the 24-hour LD cycle, are active at dawn, quieter at midday and active again at the evening, and their rhythmic behavior persists in constant dark (DD). Flies with the pdf-null (pdf01) mutation displayed disrupted circadian behavior. Locomotor activity rhythms of homozygous and hemizygous pdf01 flies were well entrained during LD cycles, but their evening activity peak was advanced by approximately 1 hr and they lacked anticipatory morning rhythms. However, in constant darkness free running rhythms were much less rhythmic than in wild type flies. [10] This demonstrates PDF’s role as a coupling factor between the M and E oscillators and its role in generating anticipation for morning rhythms.

Further research was conducted on selective ablation of the lateral ventral neurons that express the pdf gene. Fly lines with ablated PDF neurons were created using Gal4-UAS-regulated transgenes and crossing two fly lines: UAS-rpr control group or UAS-hid. Ablation did not affect the flies' ability to entrain to LD cycles, but their evening locomotor phases showed a 0.5 hour advance. This indicates the rpr and hid ablation individuals that were persistently rhythmic in DD showed shorter period length. [10] In addition, utilizing time-series immunostainings, Lin et al. showed that PDF does not function to maintain circadian rhythmicity in protein levels, but rather that it is required to coordinate rhythms among the various Drosophila pacemakers. [19] These experiments thereby confirmed the importance of the coordination role pdf expression plays in regulating circadian locomotor activity in Drosophila.

There is also evidence that the LNv neurons communicate electrically with the LNd neurons to synchronize and couple morning and evening behaviors. Wu et al.. discovered that the electrical silencing of LNv neurons by disrupting potassium gradients resulted in a phenocopy of PDF-ablated flies (pdf01), indicating that signaling from LNv neurons to LNd depends both on PDF and on electrical activity of the neurons, and that these mechanisms are not independent. [20]

In 2014, Li et al. showed that PDF synchronizes circadian clock neurons by increasing levels of cAMP and cAMP-mediated protein kinase A (PKA). [21] Increasing cAMP and PKA stabilized levels of the period protein PER in Drosophila, which slows the clock speed in PDF receptor (PDFR) containing neurons. A light pulse caused more PER degradation in flies with pdf-null neurons than flies with wild-type neurons, indicating that PDF inhibits light-induced PER degradation. [21] These experiments demonstrated that PDF interacts with secondary messenger components to coordinate circadian output.

PDF is also sufficient to induce high levels of timeless protein (TIM), another essential protein that regulates circadian rhythm. [22] Studies had found that flies with mutated ion channels at the posterior dorsal neurons 1 (DN1(p)s) showed reduced anticipatory behavior and free-running rhythms. [23] This deficit can be rescued by synapsing PDF-expressing neurons onto mutated DN1(p)s, as the elevated TIM level is enough to rescue circadian rhythm. [22]

Regulation through glia

In 2011, Ng et al. demonstrated that glial-neural signaling may physiologically modulate pdf in a calcium dependent manner. [24] The glial cells, specifically astrocytes, in the adult Drosophila brain physiologically regulate circadian neurons, and affect the output PDF. [24] Separate experiments using Gal4-UAS-regulated transgenes to alter glial release of internal calcium stores, glial vesicle trafficking, and membrane gradients all produced arrhythmic locomotor activity. [24] Immunohistochemistry staining for the peptide in the LNv dorsal projections showed a significant reduction after disruption of glial functions, suggesting that PDF transport and release are affected by glial cells. [24]

As a transcriptional regulator

A 2016 study has shown that PDF acts on E-box promoter elements of clock genes in LNv neurons to upregulate their transcription in a time-of-day dependent manner. Using fluorescent reporter genes and live cell imaging, Sabado et al. discovered that PDF upregulated CLK/CYC (two transcription factors that are a part of the oscillator that activate Per transcription) and PER expression at night, independently of its own release in the cell. This could explain further how PDF acts to synchronize the pacemaker neurons. [25]

Phylogeny

Pdf is broadly conserved across several large invertebrate clades, most notably Ecdysozoa (molting invertebrates, including arthropods) and Lophotrochozoa (annelids, mollusks, etc.), and homologs have been identified in organisms such as mosquitos and C. elegans . [6] [26] [27] PDF is not found in vertebrates, such as rodents, chimpanzees, and humans. [6]

Pdf has also been studied in the cricket Gryllus bimaculatus ; studies proved that pdf is not necessary for generating the circadian rhythm, but involved in control of nocturnal behavior, entrainment, and the fine-tuning of the free-running period of the circadian clock. [28]

Using liquid chromatography in conjunction with several biological assays, PDF, was also isolated in the insect Leucophaea maderae , a cockroach. [29]

Using Ca2+ imaging studies, researchers found two types of pacemaker cells which contained PDF in the accessory medulla, the circadian pacemaker of the cockroach, Rhyparobia maderae. Type 1 cells showed that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 cells PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. The researchers hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. This PDF-dependent depolarization could be the underlying cause of PDF-dependent phase advances of pacemaker in the cockroach. The authors proposed that PDF-dependent modulation of K+ and Na+ ion channels in coupled pacemakers causes ultradian membrane potential oscillations for efficient synchronization of pacemaker cells. [30]

Functional analog

The neuropeptide VIP is an analog of PDF instrumental for cellular and behavioral 24-hour rhythms in mammals. It is expressed in 10 percent of neurons in the SCN. [31] In a study of VIP and VIP receptor 2 (VIPR2) knockout mice, both mutants displayed entrained activity rhythms in light-dark cycle. However, in constant darkness both models displayed poor rhythmicity (very short period), and half of the animals tested were arrhythmic. [31]

VIP and PDF are functional analogs. VIP plays a role in synchronizing and supporting rhythmicity by diverse mammalian SCN pacemakers. Loss of PDF and VIP in free-running conditions resulted in similar behavioral phenotypes: dampened behavioral rhythm with a portion of the knockout mutants showing arrhythmicity. The molecular basis of these phenotypes was a loss in synchrony between pacemaker cells. Both knockout mutants show damped molecular oscillations; VIP knockouts show reduced mRNA levels, while PDF knockouts show reduced protein. Similar behavioral and molecular phenotypes are observed in loss of PDF and VIP receptors. [32]

See also

Related Research Articles

<span class="mw-page-title-main">Circadian rhythm</span> Natural internal process that regulates the sleep-wake cycle

A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximise the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.

<span class="mw-page-title-main">Suprachiasmatic nucleus</span> Part of the brains hypothalamus

The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is the principal circadian pacemaker in mammals, responsible for generating circadian rhythms. Reception of light inputs from photosensitive retinal ganglion cells allow it to coordinate the subordinate cellular clocks of the body and entrain to the environment. The neuronal and hormonal activities it generates regulate many different body functions in an approximately 24-hour cycle.

A circadian clock, or circadian oscillator, also known as one’s internal alarm clock is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

<span class="mw-page-title-main">Cryptochrome</span> Class of photoreceptors in plants and animals

Cryptochromes are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name cryptochrome was proposed as a portmanteau combining the chromatic nature of the photoreceptor, and the cryptogamic organisms on which many blue-light studies were carried out.

<span class="mw-page-title-main">CLOCK</span> Human protein and coding gene

CLOCK is a gene encoding a basic helix-loop-helix-PAS transcription factor that is known to affect both the persistence and period of circadian rhythms.

Timeless (tim) is a gene in multiple species but is most notable for its role in Drosophila for encoding TIM, an essential protein that regulates circadian rhythm. Timeless mRNA and protein oscillate rhythmically with time as part of a transcription-translation negative feedback loop involving the period (per) gene and its protein.

<span class="mw-page-title-main">GAL4/UAS system</span> Biochemical method

The GAL4-UAS system is a biochemical method used to study gene expression and function in organisms such as the fruit fly. It is based on the finding by Hitoshi Kakidani and Mark Ptashne, and Nicholas Webster and Pierre Chambon in 1988 that Gal4 binding to UAS sequences activates gene expression. The method was introduced into flies by Andrea Brand and Norbert Perrimon in 1993 and is considered a powerful technique for studying the expression of genes. The system has two parts: the Gal4 gene, encoding the yeast transcription activator protein Gal4, and the UAS, an enhancer to which GAL4 specifically binds to activate gene transcription.

<span class="mw-page-title-main">Period circadian protein homolog 1</span> Protein-coding gene in the species Homo sapiens

Period circadian protein homolog 1 is a protein in humans that is encoded by the PER1 gene.

In molecular biology, an oscillating gene is a gene that is expressed in a rhythmic pattern or in periodic cycles. Oscillating genes are usually circadian and can be identified by periodic changes in the state of an organism. Circadian rhythms, controlled by oscillating genes, have a period of approximately 24 hours. For example, plant leaves opening and closing at different times of the day or the sleep-wake schedule of animals can all include circadian rhythms. Other periods are also possible, such as 29.5 days resulting from circalunar rhythms or 12.4 hours resulting from circatidal rhythms. Oscillating genes include both core clock component genes and output genes. A core clock component gene is a gene necessary for to the pacemaker. However, an output oscillating gene, such as the AVP gene, is rhythmic but not necessary to the pacemaker.

Colin Stephenson Pittendrigh was a British-born biologist who spent most of his adult life in the United States. Pittendrigh is regarded as the "father of the biological clock," and founded the modern field of chronobiology alongside Jürgen Aschoff and Erwin Bünning. He is known for his careful descriptions of the properties of the circadian clock in Drosophila and other species, and providing the first formal models of how circadian rhythms entrain (synchronize) to local light-dark cycles.

Ronald J. Konopka (1947-2015) was an American geneticist who studied chronobiology. He made his most notable contribution to the field while working with Drosophila in the lab of Seymour Benzer at the California Institute of Technology. During this work, Konopka discovered the period (per) gene, which controls the period of circadian rhythms.

mir-279 is a short RNA molecule found in Drosophila melanogaster that belongs to a class of molecules known as microRNAs. microRNAs are ~22nt-long non-coding RNAs that post-transcriptionally regulate the expression of genes, often by binding to the 3' untranslated region of mRNA, targeting the transcript for degradation. miR-279 has diverse tissue-specific functions in the fly, influencing developmental processes related to neurogenesis and oogenesis, as well as behavioral processes related to circadian rhythms. The varied roles of mir-279, both in the developing and adult fly, highlight the utility of microRNAs in regulating unique biological processes.

<i>Cycle</i> (gene)

Cycle (cyc) is a gene in Drosophila melanogaster that encodes the CYCLE protein (CYC). The Cycle gene (cyc) is expressed in a variety of cell types in a circadian manner. It is involved in controlling both the sleep-wake cycle and circadian regulation of gene expression by promoting transcription in a negative feedback mechanism. The cyc gene is located on the left arm of chromosome 3 and codes for a transcription factor containing a basic helix-loop-helix (bHLH) domain and a PAS domain. The 2.17 kb cyc gene is divided into 5 coding exons totaling 1,625 base pairs which code for 413 aminos acid residues. Currently 19 alleles are known for cyc. Orthologs performing the same function in other species include ARNTL and ARNTL2.

<span class="mw-page-title-main">Michael Rosbash</span> American geneticist and chronobiologist (born 1944)

Michael Morris Rosbash is an American geneticist and chronobiologist. Rosbash is a professor and researcher at Brandeis University and investigator at the Howard Hughes Medical Institute. Rosbash's research group cloned the Drosophila period gene in 1984 and proposed the Transcription Translation Negative Feedback Loop for circadian clocks in 1990. In 1998, they discovered the cycle gene, clock gene, and cryptochrome photoreceptor in Drosophila through the use of forward genetics, by first identifying the phenotype of a mutant and then determining the genetics behind the mutation. Rosbash was elected to the National Academy of Sciences in 2003. Along with Michael W. Young and Jeffrey C. Hall, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".

<span class="mw-page-title-main">Jeffrey C. Hall</span> American geneticist and chronobiologist (born 1945)

Jeffrey Connor Hall is an American geneticist and chronobiologist. Hall is Professor Emeritus of Biology at Brandeis University and currently resides in Cambridge, Maine.

Paul H. Taghert is an American chronobiologist known for pioneering research on the roles and regulation of neuropeptide signaling in the brain using Drosophila melanogaster as a model. He is a professor of neuroscience in the Department of Neuroscience at Washington University in St. Louis.

<i>Drosophila</i> circadian rhythm

Drosophila circadian rhythm is a daily 24-hour cycle of rest and activity in the fruit flies of the genus Drosophila. The biological process was discovered and is best understood in the species Drosophila melanogaster. Other than normal sleep-wake activity, D. melanogaster has two unique daily behaviours, namely regular vibration during the process of hatching from the pupa, and during mating. Locomotor activity is maximum at dawn and dusk, while eclosion is at dawn.

In the field of chronobiology, the dual circadian oscillator model refers to a model of entrainment initially proposed by Colin Pittendrigh and Serge Daan. The dual oscillator model suggests the presence of two coupled circadian oscillators: E (evening) and M (morning). The E oscillator is responsible for entraining the organism’s evening activity to dusk cues when the daylight fades, while the M oscillator is responsible for entraining the organism’s morning activity to dawn cues, when daylight increases. The E and M oscillators operate in an antiphase relationship. As the timing of the sun's position fluctuates over the course of the year, the oscillators' periods adjust accordingly. Other oscillators, including seasonal oscillators, have been found to work in conjunction with circadian oscillators in order to time different behaviors in organisms such as fruit flies.

Ravi Allada is an Indian-American chronobiologist studying the circadian and homeostatic regulation of sleep primarily in the fruit fly Drosophila. He is currently the Executive Director of the Michigan Neuroscience Institute (MNI), a collective which connects neuroscience investigators across the University of Michigan to probe the mysteries of the brain on a cellular, molecular, and behavioral level. Working with Michael Rosbash, he positionally cloned the Drosophila Clock gene. In his laboratory at Northwestern, he discovered a conserved mechanism for circadian control of sleep-wake cycle, as well as circuit mechanisms that manage levels of sleep.

Jet or Jetlag is a gene discovered in Drosophila and other insects. They are a part of the SCF family of ubiquitin ligases that plays a huge role in the circadian pathway by controlling the degradation of TIM, a circadian regulatory protein. The gene plays an important role in resetting the circadian clock by transmitting light from CRY to TIM. Jetlag mutants have been found to impede re-entrainment due to significantly reduced ability to degrade TIM. The F-box protein of the FBXL family named FBXL15 is JET's mammalian homolog.

References

  1. 1 2 3 4 5 Rao KR, Riehm JP (May 1993). "Pigment-dispersing hormones". Annals of the New York Academy of Sciences. 680 (1): 78–88. Bibcode:1993NYASA.680...78R. doi: 10.1111/j.1749-6632.1993.tb19676.x . PMID   8512238. S2CID   44408395.
  2. 1 2 The Interactive Fly 2011 Apr 28.
  3. ↑ Helfrich-Förster C (2014-12-01). "From Neurogenetic Studies in the Fly Brain to a Concept in Circadian Biology". Journal of Neurogenetics. 28 (3–4): 329–347. doi:10.3109/01677063.2014.905556. ISSN   0167-7063. PMID   24655073. S2CID   38977633.
  4. 1 2 3 4 Helfrich-Förster C, Täuber M, Park JH, Mühlig-Versen M, Schneuwly S, Hofbauer A (May 2000). "Ectopic expression of the neuropeptide pigment-dispersing factor alters behavioral rhythms in Drosophila melanogaster". J. Neurosci. 20 (9): 3339–53. doi: 10.1523/JNEUROSCI.20-09-03339.2000 . PMC   6773135 . PMID   10777797.
  5. ↑ neuromodulator. (n.d.) Segen's Medical Dictionary. (2011). Retrieved April 11, 2017 from http://medical-dictionary.thefreedictionary.com/neuromodulator
  6. 1 2 3 4 National Center for Biotechnology Information: Pdf Pigment-dispersing factor (Drosophila melanogaster). 2011 Mar 29.
  7. ↑ Liang X, Holy TE, Taghert PH (2016-02-26). "Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²⁺ rhythms in vivo". Science. 351 (6276): 976–981. doi:10.1126/science.aad3997. ISSN   1095-9203. PMC   4836443 . PMID   26917772.
  8. ↑ Park JH, Hall JC (June 1998). "Isolation and chronobiological analysis of a neuropeptide pigment-dispersing factor gene in Drosophila melanogaster". J. Biol. Rhythms. 13 (3): 219–28. doi: 10.1177/074873098129000066 . PMID   9615286. S2CID   20190155.
  9. ↑ Flybase: A Database of Drosophila Genes & Genomes. 2011 Apr 27.
  10. 1 2 3 4 5 6 7 Renn SC, Park JH, Rosbash M, Hall JC, Taghert PH (December 1999). "A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila". Cell. 99 (7): 791–802. doi: 10.1016/S0092-8674(00)81676-1 . PMID   10619432. S2CID   62796150.
  11. 1 2 3 Im SH, Taghert PH (June 2010). "PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila". J. Comp. Neurol. 518 (11): 1925–1945. doi:10.1002/cne.22311. PMC   2881544 . PMID   20394051.
  12. ↑ Stoleru D, Peng Y, Nawathean P, Rosbash M (November 2005). "A resetting signal between Drosophila pacemakers synchronizes morning and evening activity". Nature. 438 (7065): 238–242. Bibcode:2005Natur.438..238S. doi:10.1038/nature04192. PMID   16281038. S2CID   4311388.
  13. ↑ Rieger D, Shafer OT, Tomioka K, Helfrich-Förster C (2006-03-01). "Functional analysis of circadian pacemaker neurons in Drosophila melanogaster". The Journal of Neuroscience. 26 (9): 2531–2543. doi: 10.1523/JNEUROSCI.1234-05.2006 . ISSN   1529-2401. PMC   6793667 . PMID   16510731.
  14. ↑ Shafer OT, Taghert PH (2009). Nitabach MN (ed.). "RNA-interference knockdown of Drosophila pigment dispersing factor in neuronal subsets: the anatomical basis of a neuropeptide's circadian functions". PLOS ONE. 4 (12): e8298. Bibcode:2009PLoSO...4.8298S. doi: 10.1371/journal.pone.0008298 . PMC   2788783 . PMID   20011537.
  15. 1 2 Lear BC, Zhang L, Allada R (2009). "The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior". PLOS Biol. 7 (7): e1000154. doi: 10.1371/journal.pbio.1000154 . PMC   2702683 . PMID   19621061.
  16. ↑ Sheeba V, Fogle KJ, Holmes TC (2010). "Persistence of morning anticipation behavior and high amplitude morning startle response following functional loss of small ventral lateral neurons in Drosophila". PLOS ONE. 5 (7): e11628. Bibcode:2010PLoSO...511628S. doi: 10.1371/journal.pone.0011628 . PMC   2905440 . PMID   20661292.
  17. 1 2 3 4 Grima B, Chélot E, Xia R, Rouyer F (14 October 2004). "Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain". Nature. 431 (7010): 869–873. Bibcode:2004Natur.431..869G. doi:10.1038/nature02935. PMID   15483616. S2CID   4394251.
  18. ↑ Shafer OT, Yao Z (2014-07-01). "Pigment-Dispersing Factor Signaling and Circadian Rhythms in Insect Locomotor Activity". Current Opinion in Insect Science. 1: 73–80. Bibcode:2014COIS....1...73S. doi:10.1016/j.cois.2014.05.002. ISSN   2214-5745. PMC   4224320 . PMID   25386391.
  19. ↑ Lin Y, Stormo GD, Taghert PH (September 2004). "The neuropeptide pigment-dispersing factor coordinates pacemaker interactions in the Drosophila circadian system". J. Neurosci. 24 (36): 7951–7957. doi: 10.1523/JNEUROSCI.2370-04.2004 . PMC   6729918 . PMID   15356209.
  20. ↑ Wu Y, Cao G, Nitabach MN (2008-04-01). "Electrical silencing of PDF neurons advances the phase of non-PDF clock neurons in Drosophila". Journal of Biological Rhythms. 23 (2): 117–128. doi: 10.1177/0748730407312984 . ISSN   0748-7304. PMID   18375861. S2CID   10010853.
  21. 1 2 Li Y, Guo F, Shen J, Rosbash M (2014). "PDF and cAMP enhance PER stability in Drosophila clock neurons". Proc Natl Acad Sci U S A. 111 (13): E1284–E1290. Bibcode:2014PNAS..111E1284L. doi: 10.1073/pnas.1402562111 . PMC   3977231 . PMID   24707054.
  22. 1 2 Seluzicki A, Flourakis M, Kula-Eversole E, Zhang L, Kilman V, Allada R, Blau J (18 March 2014). "Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior". PLOS Biology. 12 (3): e1001810. doi: 10.1371/journal.pbio.1001810 . PMC   3958333 . PMID   24643294.
  23. ↑ Zhang L, Chung BY, Lear BC, Kilman VL, Liu Y, Mahesh G, Meissner RA, Hardin PE, Allada R (April 2010). "DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila". Curr. Biol. 20 (7): 591–599. doi:10.1016/j.cub.2010.02.056. PMC   2864127 . PMID   20362452.
  24. 1 2 3 4 Ng FS, Tangredi MM, Jackson FR (April 2011). "Glial cells physiologically modulate clock neurons and circadian behavior in a calcium-dependent manner". Curr. Biol. 21 (8): 625–634. Bibcode:2011CBio...21..625N. doi:10.1016/j.cub.2011.03.027. PMC   3081987 . PMID   21497088.
  25. ↑ Sabado V, Vienne L, Nunes JM, Rosbash M, Nagoshi E (2017-01-30). "Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock". Scientific Reports. 7: 41560. Bibcode:2017NatSR...741560S. doi:10.1038/srep41560. ISSN   2045-2322. PMC   5278502 . PMID   28134281.
  26. ↑ Mayer G, Hering L, Stosch JM, Stevenson PA, Dircksen H (September 2015). "Evolution of pigment-dispersing factor neuropeptides in panarthropoda: Insights from onychophora (velvet worms) and tardigrada (water bears)". Journal of Comparative Neurology. 523 (13): 1865–1885. doi:10.1002/cne.23767. ISSN   0021-9967. PMID   25722044. S2CID   19580965.
  27. ↑ Martin C, Hering L, Metzendorf N, Hormann S, Kasten S, Fuhrmann S, Werckenthin A, Herberg FW, Stengl M, Mayer G (2020). "Analysis of Pigment-Dispersing Factor Neuropeptides and Their Receptor in a Velvet Worm". Frontiers in Endocrinology. 11: 273. doi: 10.3389/fendo.2020.00273 . ISSN   1664-2392. PMC   7235175 . PMID   32477266.
  28. ↑ Hassaneen E, El-Din Sallam A, Abo-Ghalia A, Moriyama Y, Karpova SG, Abdelsalam S, Matsushima A, Shimohigashi Y, Tomioka K (February 2011). "Pigment-dispersing factor affects nocturnal activity rhythms, photic entrainment, and the free-running period of the circadian clock in the cricket gryllus bimaculatus". J. Biol. Rhythms. 26 (1): 3–13. CiteSeerX   10.1.1.1013.3309 . doi:10.1177/0748730410388746. PMID   21252361. S2CID   26698831.
  29. ↑ Hamasaka Y, Mohrherr CJ, Predel R, Wegener C (2005). "Chronobiological analysis and mass spectrometric characterization of pigment-dispersing factor in the cockroach Leucophaea maderae". J. Insect Sci. 5: 43. doi:10.1093/jis/5.1.43. PMC   1615250 . PMID   17119625.
  30. ↑ Wei H, Yasar H, Funk NW, Giese M, Baz ES, Stengl M, Yamazaki S (30 September 2014). "Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae". PLOS ONE. 9 (9): e108757. Bibcode:2014PLoSO...9j8757W. doi: 10.1371/journal.pone.0108757 . PMC   4182629 . PMID   25269074.
  31. 1 2 Im SH, Taghert PH (1 June 2010). "PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila". The Journal of Comparative Neurology. 518 (11): 1925–1945. doi:10.1002/cne.22311. PMC   2881544 . PMID   20394051.
  32. ↑ Vosko AM, Schroeder A, Loh DH, Colwell CS (June 2007). "Vasoactive intestinal peptide and the mammalian circadian system". General and Comparative Endocrinology. 152 (2–3): 165–175. doi:10.1016/j.ygcen.2007.04.018. PMC   1994114 . PMID   17572414.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.