[2] 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.
[5] Pigment dispersing factor (pdf) was first discovered in the central nervous system of arthropods by K. Ranga Rao and John P. Riehm in 1993.
Helfrich-Forster discovered that misexpressing pdf in neurons with dorsal and central brain axon terminals affected activity rhythms.
The laboratories of Paul H. Taghert, Jeff Hall, and Michael Rosbash identified a null allele of the pdf gene.
[6] Recently, the Taghert lab reported that each of the five major pacemaker groups in the fly brain exhibits a daily large calcium transient.
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.
It is believed that the reset signal is PDF, because it is M-cell specific and plays a large role in maintaining normal rhythmicity.
[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.
[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.
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.
Ablation did not affect the flies' ability to entrain to LD cycles, but their evening locomotor phases showed a 0.5 hour advance.
[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.
[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.
[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.
[24] The glial cells, specifically astrocytes, in the adult Drosophila brain physiologically regulate circadian neurons, and affect the output PDF.
[24] 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.
[28] Using liquid chromatography in conjunction with several biological assays, PDF, was also isolated in the insect Leucophaea maderae, a cockroach.
In contrast, in type 2 cells PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity.