Pigment dispersing factor

Unknown parameter FlyBase Unknown parameter FlyBase Pigment dispersing factor (pdf) is a gene that encodes the protein PDF, which is part of a large family of neuropeptides. 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. The movement and aggregation of pigments in retina cells and extra-retinal cells is hypothesized to be under a split hormonal control mechanism. 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. However, insect pdf genes do not function in such pigment migration since they lack the chromatophore. 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. 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. 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. 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. 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. 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. In Drosophila, the pdf gene is intronless and is located at 97B on the third chromosome. It exists in a single copy per haploid genome and the approximately 0.8 kb transcript is expressed in the Drosophila's head. The cDNA clone in flies has 1080 base pairs with a single exon. 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. 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. 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.