A Database for Insect Neuropeptide Research

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Insect Neuropeptides - Pigment-dispersing factor


Pigment-dispersing hormones (PDHs) were identified in eyestalks of crustaceans as the factor that disperses dark pigment in chromatophores, and induces pigment movements in the eye in response to light (Rao and Riehm, 1988, 1993). A similar octadecapeptide was isolated from the grasshopper Romalea microptera (Rao et al., 1987). This insect peptide was named pigment-dispersing factor (PDF). A first PDH precursor gene was cloned in a crab (Klein et al., 1994) and later a PDF gene (CG6496) was identified in Drosophila (Park and Hall, 1998). The Drosophila precursor contains one copy of PDF with the sequence NSELINSLLSLPKNMNDAamide. This sequence is fairly well conserved throughout the insects studied. The PDF receptor in Drosophila (CG13758) is a class B (class II) GPCR related to the PACAP/VIP receptors in mammals (Mertens et al., 2005).


PDF is produced in small sets of brain neurons and abdominal neurosecretory cells in most insects studied (Homberg et al., 1991; Nässel et al., 1991, 1993). It was found that a set of PDF-producing neurons in the brain of Drosophila co-localizes the clock gene period (Helfrich-Förster, 1995), and thus intense research into the role of PDF in clock function started (see below). The abdominal neurosecretory cells have axons that terminate on the hindgut in flies and locusts (Nässel et al., 1993; Persson et al. 2001).


The PDF expressing clock neurons in the Drosophila brain are named small lateral ventral neurons (s-LNv) and large lateral ventral neurons (l-LNv) and have been extensively investigated for their role in clock functions and sleep (Hardin, 2005; Taghert and Nitabach, 2012). PDF released from these clock neurons is critical for intact rhythm generation of the circadian clock network in the brain (Renn et al., 1999; Shafer and Taghert, 2009; Shafer et al., 2008). Also in the cockroach Leucophaea (Rhyparobia) maderae PDF plays an important role in the circadian clock (Wei et al., 2014). Accessory to the clock function of PDF, it was shown that PDF in the sLNv neurons, together with neuropeptide F neurons, controls rival-induced prolonged mating in Drosophila in a sex-dimorphic fashion (Kim et al., 2013). A peripheral role of PDF was suggested from the expression of this peptide in neurosecretory cells of abdominal ganglia in Drosophila and other insects, and the presence of PDF in locust haemolymph (Nässel et al., 1993; Persson et al. 2001). In Drosophila PDF stimulates contractions in the renal tubules in a cyclic AMP dependent fashion (Talsma et al., 2012). The renal tubules are not innervated by PDF neurons, suggesting that the PDF action is hormonal. These authors propose that PDF, like its mammalian relative vasoactive intestinal peptide (VIP), have dual functions as regulators of brain neurons and visceral muscle. The PDF neurons also signal to the oenocytes in the body wall and modulate the phase of the oenocyte clock and thereby regulate male sex pheromone production (Krupp et al., 2013). Thus centrally derived PDF can modulate peripheral clock function. Furthermore, a genetic screen identified the PDF receptor in specific sets of neurons as an important regulator of flight in Drosophila (Agrawal et al., 2013). It was proposed that PDF acts in integration of sensory inputs and modulation of downstream motoneuron activity in generation of flight. Finally, it was shown in Bombyx mori that PDF stimulates ecdysone biosynthesis via the PDF receptor BNGR-B2 in a partial overlap with PTTH (Iga et al., 2014).

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Suggested Reviews

  • Hardin PE. 2005. The circadian timekeeping system of Drosophila. Curr Biol 15(17):R714-722.
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  • Rao KR, Riehm JP. 1993. Pigment-dispersing hormones. Annals of the New York Academy of Sciences 680:78-88.
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  • Taghert PH, Nitabach MN. 2012. Peptide neuromodulation in invertebrate model systems. Neuron 76(1):82-97.
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  • Agrawal, T., Sadaf, S., and Hasan, G. (2013). A genetic RNAi screen for IP(3)/Ca(2)(+) coupled GPCRs in Drosophila identifies the PdfR as a regulator of insect flight. PLoS genetics 9(10), e1003849. doi:10.1371/journal.pgen.1003849.
  • Homberg U, Würden S, Dircksen H, Rao KR. 1991. Comparative anatomy of pigment-dispersing hormone-immunoreactive neurons in the brain of orthopteroid insects. Cell Tissue Res 266:343–357.
  • Iga, M., Nakaoka, T., Suzuki, Y., and Kataoka, H. (2014). Pigment dispersing factor regulates ecdysone biosynthesis via bombyx neuropeptide G protein coupled receptor-B2 in the prothoracic glands of Bombyx mori. PLoS ONE 9(7), e103239. doi: 10.1371/journal.pone.0103239.
  • Kim WJ, Jan LY, Jan YN. 2013. A PDF/NPF neuropeptide signalling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating. Neuron 80(5):1190-1205.
  • Krupp, J.J., Billeter, J.C., Wong, A., Choi, C., Nitabach, M.N., and Levine, J.D. (2013). Pigment-dispersing factor modulates pheromone production in clock cells that influence mating in Drosophila. Neuron 79(1), 54-68. doi: 10.1016/j.neuron.2013.05.019.
  • Mertens I, Vandingenen A, Johnson EC, Shafer OT, Li W, Trigg JS, De Loof A, Schoofs L, Taghert PH. 2005. PDF receptor signalling in Drosophila contributes to both circadian and geotactic behaviours. Neuron 48(2):213-219.
  • Nässel DR, Shiga S, Mohrherr CJ, Rao KR. 1993. Pigment-dispersing hormone-like peptide in the nervous system of the flies Phormia and Drosophila: immunocytochemistry and partial characterization. The Journal of comparative neurology 331(2):183-198.
  • Persson MG, Eklund MB, Dircksen H, Muren JE, Nässel DR. 2001. Pigment-dispersing factor in the locust abdominal ganglia may have roles as circulating neurohormone and central neuromodulator. J Neurobiol 48(1):19-41.
  • Rao KR, Riehm JP. 1988. Pigment-dispersing hormones: a novel family of neuropeptides from arthropods. Peptides 9 Suppl 1:153-159.
  • Rao KR, Riehm JP. 1993. Pigment-dispersing hormones. Annals of the New York Academy of Sciences 680:78-88.
  • Renn SC, Park JH, Rosbash M, Hall JC, Taghert PH. 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.
  • Shafer OT, Taghert PH. 2009. 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. Shafer OT, Kim DJ, Dunbar-Yaffe R, Nikolaev VO, Lohse MJ, Taghert PH. 2008. Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging. Neuron 58(2):223-237.
  • Talsma AD, Christov CP, Terriente-Felix A, Linneweber GA, Perea D, Wayland M, Shafer OT, Miguel-Aliaga I. 2012. Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila. Proc Natl Acad Sci U S A 109(30):12177-12182.
  • Wei H, Yasar H, Funk NW, Giese M, Baz el S, Stengl M. 2014. Signalling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae. PLoS ONE 9(9):e108757.