Behavior Genetics

, Volume 35, Issue 3, pp 231–244 | Cite as

Drosophila soluble guanylyl cyclase mutants exhibit increased foraging locomotion: behavioral and genomic investigations

  • Craig A. L. Riedl
  • Scott J. Neal
  • Alain Robichon
  • J. Timothy Westwood
  • Marla B. Sokolowski
Article

Genetic variation in the gene foraging (for) is associated with a natural behavioral dimorphism in the fruit fly, Drosophila melanogaster. Some larvae, called ‘rovers’, have increased foraging locomotion compared to others, called ‘sitters’, and this difference is directly related to for-encoded cGMP-dependent protein kinase (PKG) activity. Here we report that larvae with mutations in the gene dgcα1, which encodes a soluble guanylyl cyclase (sGC) subunit, have increases in both PKG activity and foraging locomotion. This is contrary to our original prediction that, based on the role of sGC in the synthesis of cGMP, dgcα1 mutant larvae would have deficient cGMP production leading to decreased PKG activation and thus reduced larval foraging locomotion. We performed DNA microarray analyses to compare transcriptional changes induced by a dgcα1 mutation in both rover and sitter wildtype genetic backgrounds. In either background, we identified many genes that are differentially transcribed, and interestingly, relatively few are affected in both backgrounds. Furthermore, several of these commonly affected genes are enhanced or suppressed in a background-dependent manner. Thus, genetic background has a critical influence on the molecular effects of this mutation. These findings will support future investigations of Drosophila foraging behavior.

KEYWORDS:

behavior cGMP Drosophila foraging guanylyl cyclase genetic background microarray. 

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References

  1. Anholt, R. R., Mackay, T. F. C. 2004Quantitative genetic analyses of complex behaviours in DrosophilaNat. Rev. Genet.5838849PubMedGoogle Scholar
  2. Ball, E. E., Truman, J. W. 1998Developing grasshopper neurons show variable levels of guanylyl cyclase activity on arrival at their targetsJ. Comp. Neurol.394113PubMedGoogle Scholar
  3. Bourne, H. R., Nicoll, R. 1993Molecular machines integrate coincident synaptic signalsCell726575PubMedGoogle Scholar
  4. Casnellie, J. E. 1991Assay of protein kinases using peptides with basic residues for phosphocellulose bindingMethods Enzymol.200115120PubMedGoogle Scholar
  5. Cheung, B. H., Arellano-Carbajal, F., Rybicki, I., De Bono, M. 2004Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behaviorCurr. Biol.1411051111PubMedGoogle Scholar
  6. de Belle, J. S., Heisenberg, M. 1996Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: a case study of the mushroom body miniature gene (mbm)Proc. Natl. Acad. Sci. USA9398759880PubMedGoogle Scholar
  7. de Belle, J. S., Hilliker, A. J., Sokolowski, M. B. 1989Genetic localization of foraging (for): a major gene for larval behavior in Drosophila melanogaster Genetics123157163PubMedGoogle Scholar
  8. Drain, P., Folkers, E., Quinn, W. G. 1991cAMP-dependent protein kinase and the disruption of learning in transgenic fliesNeuron67182PubMedGoogle Scholar
  9. Dubnau, J., Tully, T. 1998Gene discovery in Drosophila: new Insights for Learning and MemoryAnnu. Rev. Neurosci.21407444PubMedGoogle Scholar
  10. Eisen, M. B., Spellman, P. T., Brown, P. O., Botstein, D. 1998Cluster analysis and display of genome-wide expression patternsProc. Natl. Acad. Sci. USA951486314868PubMedGoogle Scholar
  11. Elphick, M. R., Jones, I. W. 1998Localization of soluble guanylyl cyclase α-subunit in identified insect neuronsBrain Res.800174179PubMedGoogle Scholar
  12. Fiscus, R. R., Murad, F. 1988cGMP-dependent protein kinase activation in intact tissuesMethods Enzymol.159150159CrossRefPubMedGoogle Scholar
  13. Garbers, D. L. 1999The guanylyl cyclase receptorsMethods19477484PubMedGoogle Scholar
  14. Gerlai, R. 1996Gene-targeting studies of mammalian behavior: is it the mutations or the background genotype?Trends Neurosci.19177181PubMedGoogle Scholar
  15. Gibbs, S. M., Becker, A., Hardy, R. W., Truman, J. W. 2001Soluble guanylate cyclase is required during development for visual system function in DrosophilaJ. Neurosci.2177057714PubMedGoogle Scholar
  16. Gim, B. S., Park, J. M., Yoon, J. H., Kang, C., Kim, Y. J. 2001Drosophila Med6 is required for elevated expression of a large but distinct set of developmentally regulated genesMol. Cell. Biol.2152425255PubMedGoogle Scholar
  17. Graf, S. A., Sokolowski, M. B. 1989Rover/sitter Drosophila melanogaster larval foraging polymorphism as a function of larval development, food-patch quality, and starvationJ. Insect Behav.2301313Google Scholar
  18. Gray, J. M., Karow, D. S., Lu, H., Chang, A. J., Chang, J. S., Ellis, R. E., Marletta, M. A., Bargmann, C. I. 2004Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologueNature430317322PubMedGoogle Scholar
  19. Greenspan, R. J. 1997A kinder, gentler genetic analysis of behavior: dissection gives way to modulationCurr. Opin. Neurobiol.7805811PubMedGoogle Scholar
  20. Hardman, J. G., Sutherland, E. W. 1969Guanyl Cyclase, an enzyme catalyzing the formation of guanosine 3′,5′-monophosphate from guanosine triphosphateJ. Biol. Chem.24463636370PubMedGoogle Scholar
  21. Jin, W., Riley, R. M., Wolfinger, R. D., White, K. P., Passador-Gurgel, G., Gibson, G. 2001The contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster Nat. Genet.29389395PubMedGoogle Scholar
  22. Kalderon, D., Rubin, G. M. 1989cGMP-dependent protein kinase genes in DrosophilaJ. Biol. Chem.2641073810748PubMedGoogle Scholar
  23. Koesling, D. 1998Modulators of soluble guanylyl cyclaseNaunyn Schmiedebergs Arch. Pharmacol.358123126PubMedGoogle Scholar
  24. Koesling, D., Russwurm, M., Mergia, E., Mullershausen, F., Friebe, A. 2004Nitric oxide-sensitive guanylyl cyclase: structure and regulationNeurochem. Int.45813819PubMedGoogle Scholar
  25. LaGraize, S. C., Borzan, J., Rinker, M. M., Kopp, J. L., Fuchs, P. N. 2004Behavioral evidence for competing motivational drives of nociception and hungerNeurosci. Lett.3723034PubMedGoogle Scholar
  26. Langlais, K. K., Stewart, J. A., Morton, D. B. 2004Preliminary characterization of two atypical soluble guanylyl cyclases in the central and peripheral nervous system of Drosophila melanogaster J. Exp. Biol.20723232338PubMedGoogle Scholar
  27. Lee, J., Kim, S. W., Jung, T. K., Oh, Y., Park, C. S., Ma, S. K., Kim, N. H., Choi, K. C. 2004Indomethacin decreases particulate guanylyl cyclase activity in rat kidneyClin. Exp. Pharmacol. Physiol.31207211PubMedGoogle Scholar
  28. Lindsey, D. L., Zimm, G. G. 1992The genome of Drosophila MelanogasterAcademic PressNY, USAGoogle Scholar
  29. Liu, W., Yoon, J., Burg, M., Chen, L., Pak, W. L. 1995Molecular characterization of two Drosophila guanylate cyclases expressed in the nervous systemJ. Biol. Chem.2701241812427PubMedGoogle Scholar
  30. Lucas, K. A., Pitari, G. M., Kazerounian, S., Ruiz-Stewart, I., Park, J., Schultz, S., Chepenik, K. P., Waldman, S. A. 2000Guanylyl cyclases and signaling by cyclic GMPPharmacol. Rev.52375413PubMedGoogle Scholar
  31. Morton, D. B. 2004aInvertebrates yield a plethora of atypical guanylyl cyclasesMol. Neurobiol.2997115Google Scholar
  32. Morton, D. B. 2004bAtypical soluble guanylyl cyclases in Drosophila can function as molecular oxygen sensorsJ. Biol. Chem.2795065150653Google Scholar
  33. Müller, U., Hildebrandt, H. 2002Nitric oxide/cGMP-mediated protein kinase A activation in the antennal lobes plays an important role in appetitive reflex habituation in the honeybeeJ. Neurosci.2287398747PubMedGoogle Scholar
  34. Neal, S. J., Gibson, M. L., So, A. K.-C., Westwood, J. T. 2003Construction of a cDNA-based microarray for Drosophila melanogaster: a comparison of gene transcription profiles from SL2 and Kc167 cellsGenome46879892PubMedGoogle Scholar
  35. Nighorn, A., Byrnes, K. A., Morton, D. B. 1999Identification and characterization of a novel β subunit of soluble guanylyl cyclase that is active in the absence of a second subunit and is relatively insensitive to nitric oxideJ. Biol. Chem.27425252531PubMedGoogle Scholar
  36. Nighorn, A., Gibson, N. J., Rivers, D. M., Hildebrand, J. G., Morton, D. B 2000The nitric oxide-cGMP pathway may mediate communication between sensory afferents and projection neurons in the antennal lobe of Manduca sexta J. Neurosci.1872447255Google Scholar
  37. Osborne, K. A., Robichon, A., Burgess, E., Butland, S., Shaw, R. A., Coulthard, A., Pereira, H. S., Greenspan, R. J., Sokolowski, M. B. 1997Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila Science277 834836PubMedGoogle Scholar
  38. Pelligrino, D. A., Wang, Q. 1998Cyclic nucleotide crosstalk and the regulation of cerebral vasodilationProg. Neurobiol.56118PubMedGoogle Scholar
  39. Pereira, H. S., MacDonald, D. E., Hilliker, A. J., Sokolowski, M. B. 1995Chaser (Csr), a new gene affecting larval foraging behavior in Drosophila melanogaster Genetics141263270PubMedGoogle Scholar
  40. Prabhakar, S., Short, D. B., Scholz, N. L., Goy, M. F. 1997Identification of nitric oxide-sensitive and -insensitive forms of cytoplasmic guanylate cyclaseJ. Neurochem.6916501660PubMedCrossRefGoogle Scholar
  41. Ramakers, C., Ruijter, J. M., Lekanne Deprez, R. H., Moorman, A. F. M. 2003Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) dataNeurosci. Lett.3396266PubMedGoogle Scholar
  42. Redkozubov, A. 2000Guanosine 3′,5′-cyclic monophosphate reduces the response of the Moth’s olfactory receptor neuron to pheromoneChem. Senses.25381385PubMedGoogle Scholar
  43. Rivero-Vilches, F. J., de Frutos, S., Saura, M., Rodriguez-Puyol, D., Rodriguez-Puyol, M. 2003Differential relaxing responses to particulate or soluble guanylyl cyclase activation on endothelial cells: a mechanism dependent on PKG-I alpha activation by NO/cGMPAm. J. Physiol. Cell Physiol.285C891C898PubMedGoogle Scholar
  44. Rozen, S., Skaletsky, H. 2000Primer3 on the WWW for general users and for biologist programmersMethods Mol. Biol.132365386PubMedGoogle Scholar
  45. Sambrook, J., Russell, D. 2001Molecular cloning. A laboratory manual3Cold Spring Harbor Laboratory PressCold Spring Harbor, NY, USAGoogle Scholar
  46. SAS Institute Inc.1999SAS/STAT user’s guide, version 8SAS Institute IncCary, NCGoogle Scholar
  47. Shah, S., Hyde, D. R. 1995Two Drosophila genes that encode the α and β subunits of the brain soluble guanylyl cyclaseJ. Biol. Chem.2701536815376PubMedGoogle Scholar
  48. Shaver, S. A., Riedl, C. A. L., Parkes, T. L., Sokolowski, M. B., Hilliker, A. J. 2000Isolation of larval behavioral mutants in Drosophila melanogaster J. Neurogenet.14193205PubMedGoogle Scholar
  49. Sokolowski, M. B. 1980Foraging strategies of Drosophila melanogaster: a chromosomal analysisBehav. Genet.10291302PubMedGoogle Scholar
  50. Sokolowski, M. B. 2001Drosophila: genetics meets behaviourNat. Rev. Genet.2879890PubMedGoogle Scholar
  51. Sokolowski, M. B., Pereira, H. S., Hughes, K. 1997Evolution of foraging behavior in Drosophila by density-dependent selectionProc. Natl. Acad. Sci. USA9473737377PubMedGoogle Scholar
  52. Sokolowski, M .B., Riedl, C. A. L. 1999

    Behaviour-genetic and molecular analysis of naturally occurring variation in Drosophila larval foraging behaviour

    Gerlai, R.Crusio, W. eds. Molecular-genetic techniques for brain and behaviourElsevier ScientificLondon517532
    Google Scholar
  53. Stone, J. R., Marletta, M. A. 1994Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric statesBiochemistry3356365640PubMedGoogle Scholar
  54. Truman, J. W., De Vente, J., Ball, E. E. 1996Nitric oxide-sensitive guanylate cyclase activity is associated with the maturational phase of neuronal development in insectsDevelopment12239493958PubMedGoogle Scholar
  55. Tully, T. 1996Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectivesProc. Natl. Acad. Sci. USA931346013467PubMedGoogle Scholar
  56. Tusher, V. G., Tibshirani, R., Chu, G. 2001Significance analysis of microarrays applied to the ionizing radiation responseProc. Natl. Acad. Sci. USA9851165121PubMedGoogle Scholar
  57. Wang, X., Robinson, P. J. 1997Cyclic GMP-dependent protein kinase and cellular signaling in the nervous systemJ. Neurochem.68443456PubMedCrossRefGoogle Scholar
  58. Wedel, B. J., Garbers, D. L. 2001The guanylyl cyclase family at Y2KAnnu. Rev. Physiol.63215233PubMedGoogle Scholar
  59. Wildemann, B., Bicker, G. 1999aDevelopmental expression of nitric oxide/cyclic GMP synthesizing cells in the nervous system of Drosophila melanogaster J. Neurobiol.38115Google Scholar
  60. Wildemann, B., Bicker, G. 1999bNitric oxide and cyclic GMP induce vesicle release at Drosophila neuromuscular junctionJ. Neurobiol.39337346Google Scholar
  61. Yoshikawa, S., Miyamoto, I., Aruga, J., Furuichi, T., Okano, H., Mikoshiba, K. 1993Isolation of a Drosophila gene encoding a head-specific guanylyl cyclaseJ. Neurochem.6015701573PubMedGoogle Scholar
  62. Zhang, L., Tinette, S., Robichon, A. 2002Drosophila NO-dependent guanylyl cyclase is finely regulated by sequential order of coincidental signalingJ. Cell. Biochem.85392402PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Craig A. L. Riedl
    • 1
  • Scott J. Neal
    • 1
    • 2
  • Alain Robichon
    • 3
  • J. Timothy Westwood
    • 1
    • 2
  • Marla B. Sokolowski
    • 1
  1. 1.Department of BiologyUniversity of Toronto at MississaugaMississaugaCanada
  2. 2.Canadian Drosophila Microarray Centre, Department of BiologyUniversity of Toronto at MississaugaMississaugaCanada
  3. 3.INRA Centre de Recherche de Sophia-AntipolisSophia-Antipolis CedexFrance

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