Skip to main content
SpringerLink
Log in

Circadian Timekeeping in Drosophila

  • Chapter
Circadian Clocks

Part of the book series: Handbook of Behavioral Neurobiology ((HBNE,volume 12))

  • 649 Accesses

Abstract

This chapter, written in the spring of 1997, describes the first two clock genes to be characterized in Drosophila.A study of the interactions of period and timeless pointed to a simple mechanism that generates self-sustained molecular oscillations, but that can be reset by exposure to cycles of day and night. Four years later, it is remarkable to see how quickly answers to many of the questions posed in this chapter have emerged. Missing pieces of the clock have been found, and insights from the fruit fly have allowed molecular dissection of human cycles of sleep and wakefulness.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aronson, B. D., Johnson, K. A., Loros, J. J., & Dunlap, J. C. (1994). Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science, 263, 1578–1584.

    Article  PubMed  CAS  Google Scholar 

  • Bargiello, T. A., &Young, M. W. (1984). Molecular genetics of a biological clock in Drosophila. Proceedings of the National Academy of Sciences of the USA, 81, 2142–2146.

    Article  PubMed  CAS  Google Scholar 

  • Bargiello, T. A., Jackson, E R., & Young, M. W. (1984). Restoration of circadian behavioral rhythms by gene transfer in Drosophila. Nature, 312, 752–754.

    Article  PubMed  CAS  Google Scholar 

  • Baylies, M. K., Bargiello, T. A., Jackson, F. R., and Young, M. W. (1987). Changes in abundance or structure of the per gene product can affect periodicity of the Drosophila clock. Nature, 326, 390–392.

    Article  PubMed  CAS  Google Scholar 

  • Borjigin, J., Wang, M. M., and Snyder, S. H. (1995). Diurnal variation in mRNA encoding serotonin Nacetyltransferase in pineal gland. Nature, 378, 783–785.

    Article  PubMed  CAS  Google Scholar 

  • Burbach, K. M., Poland, A., & Bradfield, C. A. (1992). Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proceedings of the National Academy of Sciences of the USA, 89, 8185–8189.

    Article  PubMed  CAS  Google Scholar 

  • Citri, Y. V., Colot, H. V., Jacquier, A. C., Yu, Q., Hall, J. C., Baltimore, D., & Rosbash, M. (1987). A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene. Nature, 326, 42–47.

    Article  PubMed  CAS  Google Scholar 

  • Coon, S. L., Roseboom, P. H., Ruben, B., Weller, J. L., Namboodiri, M. A. A., Koonin, E. V., & Klein, D. C. (1995). Pineal serotonin Nacetyltransferase: Expression cloning and molecular analysis. Science, 270, 1681–1683

    Article  PubMed  CAS  Google Scholar 

  • Cote, G. C., & Brody, S. (1986). Circadian rhythms in D. melanogaster. Analysis of period as a function of gene dosage at the per (period) locus. Journal of Theoretical Biology, 121, 487–503.

    Article  PubMed  CAS  Google Scholar 

  • Crews, S. T., Thomas, J. B., & Goodman, C. S. (1988). The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product. Cell, 52, 143–151.

    Article  PubMed  CAS  Google Scholar 

  • Crosthwaite, S. K., Loros, J. J., & Dunlap, J. C. (1995). Light-induced resetting of a circadian clock is mediated by a rapid increase in frequency transcript. Cell, 81, 1003–1012.

    Article  PubMed  CAS  Google Scholar 

  • Curtin, K. D., Huang, Z. J., & Rosbash, M. (1995). Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock. Neuron, 14, 365–372.

    Article  PubMed  CAS  Google Scholar 

  • Edery, I., Zweibel, L. J., Dembinska, M. E., & Rosbash, M. (1994). Temporal phosphorylation of the Drosophila period protein. Proceedings of the National Academy of Sciences of the USA, 91, 2260–2264.

    Article  PubMed  CAS  Google Scholar 

  • Emery, I. F., Noveral, J. M., Jamison, C. E, and Siwicki, K. K., (1997). Rhythms of Drosophila period gene expression in culture. Proceedings of the National Academy of Sciences of the USA, 94, 4092–4096.

    Article  Google Scholar 

  • Ewer, J., Frisch, B., Hamblen-Coyle, M. J., Rosbash, M., & Hall, J. C. (1992). Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of the cells’ influence on circadian behavioral rhythms. Journal of Neuroscience, 12, 3321–3349.

    PubMed  CAS  Google Scholar 

  • Feldman, J. F., & Hoyle, M. N. (1973). Isolation of circadian clock mutants of Neurospora crassa. Genetics, 75, 605–613.

    PubMed  CAS  Google Scholar 

  • Foulkes, N. S., Duval, G., and Sassone-Corsi, P. (1996). Adaptive inducibility of CREM as transcriptional memory of circadian rhythms. Nature, 381, 83–85

    Article  PubMed  CAS  Google Scholar 

  • Frisch, B., Hardin, P. E., Hamblen-Coyle, M. J., Rosbash, M., & Hall, J. C. (1994). A promoterless period gene mediates behavioral rhythmicity and cyclical per expression in a restricted subset of the Drosophila Nervous system. Neuron, 12, 555–570.

    Article  PubMed  CAS  Google Scholar 

  • Gekakis, N., Saez, L., Delahaye-Brown, A-M., Myers, M. P., Sehgal, A., Young, M. W., Sc Weitz, C. J. (1995). Isolation of timeless by PER protein interaction: Defective interaction between timeless protein and long-period Mutant PERL. Science, 270, 811–815.

    Article  PubMed  CAS  Google Scholar 

  • Giebultowicz, J. M. & Hege, D. M. (1997). Circadian clock in malphigian tubules. Nature, 386, 664.

    Article  PubMed  CAS  Google Scholar 

  • Giuliano, G., Hoffman, N. E., Ko, K., Scolnik, P. A., & Cashmore, A. R. (1988). A light-entrained circadian clock controls transcription of several plant genes. EMBO Journal. 7, 3635–3642.

    PubMed  CAS  Google Scholar 

  • Hall, J. C. (1996). Are cycling gene products as internal zeitgebers no longer the zeitgeist of chronobiology? Neuron, 17, 799–802.

    Article  PubMed  CAS  Google Scholar 

  • Handler, A. M., & Konopka, R. J. (1979). Transplantation of a circadian pacemaker in Drosophila. Nature, 279, 236–238.

    Article  PubMed  CAS  Google Scholar 

  • Hardin, P. E. (1994). Analysis of period mRNA cycling in Drosophila head and body tissues indicates that body oscillators behave differently from head oscillators. Molecular and Cellular Biology, 14, 7211–7218.

    PubMed  CAS  Google Scholar 

  • Hardin, P. E., Hall, J. C., & Rosbash, M. (1990). Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature, 343, 536–540.

    Article  PubMed  CAS  Google Scholar 

  • Hardin, P. E., Hall, J. C., & Rosbash, M. (1992). Circadian oscillations in period gene mRNA levels are transcriptionally regulated. Proceedings of the National Academy of Sciences of the USA, 89, 11711–11715.

    Article  PubMed  CAS  Google Scholar 

  • Hoffman, E. C., Reyes, J., Chu, F. F., Sander, F., Conley, L. H., Brooks, B. A., & Hankinson, O. (1991). Cloning of a factor required for activity of the Ah (dioxin) receptor. Science, 252, 954–958.

    Article  PubMed  CAS  Google Scholar 

  • Huang, Z. J., Edery, I., & Rosbash, M. (1993). PAS is a dimerization domain common to Drosophila period and several transcription factors. Nature, 364, 259–262.

    Article  Google Scholar 

  • Hunter-Ensor, M., Ousley, A., & Sehgal, A. (1996). Regulation of the Drosophila protein Timeless suggests a mechanism for resetting the circadian clock by light. Cell, 84, 677–685.

    Article  PubMed  CAS  Google Scholar 

  • Jackson, F. R., Bargiello, T. A., Yun, S.-H., & Young, M. W. (1986). Product of perlocus of Drosophila shares homology with proteoglycans. Nature 320, 185–188.

    Article  PubMed  CAS  Google Scholar 

  • Konopka, R. J., Sc Benzer, S. (1971). Clock mutants of Drosophila melanogaster. Proceedings of the National Academy of Sciences of the USA, 68, 2112–2116.

    Article  PubMed  CAS  Google Scholar 

  • Konopka, R. J. (1981). Genetics and development of circadian rhythms in invertebrates. In J. Aschoff (Ed.), Handbook of behavioral neurobiology (pp. 173–182). New York: Plenum Press.

    Google Scholar 

  • Konopka, R. J., Wells, S., and Lee, T. (1983). Mosaic analysis of a Drosophila clock mutant. Molecular and General Genetics, 190, 284–288.

    Article  Google Scholar 

  • Konopka, R. J., Pittendrigh, C. S., & Orr, D. (1989). Reciprocal behavior associated with altered homeo-stasis and photosensitivity of Drosophila clock mutants. Journal of Neurogenetics, 6, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Korenbrot, J. I., & Fernald, R. D. (1989). Circadian rhythm and light regulate opsin mRNA in rod photoreceptors. Nature, 337, 454–457.

    Article  PubMed  CAS  Google Scholar 

  • Lee, C., Parikh, V., Itsukaichi, T., Bae, K., & Edery, I. (1996). Resetting the Drosophila clock by photic regulation of PER and PER-TIM complex. Science, 271, 1740–1744.

    Article  PubMed  CAS  Google Scholar 

  • Liu, X., Lorenz, L. J., Yu, Q., Hall, J. C., & Rosbash, M. (1988). Spatial and temporal expression of the per gene in D. melanogaster. Genes and Development, 2, 228–238.

    Article  PubMed  CAS  Google Scholar 

  • Liu, X., Zweibel, L. J., Hinton, D., Benzer, S., Hall, J. C., & Rosbash, M. (1992). The period gene encodes a predominantly nuclear protein in adult Drosophila. Journal of Neuroscience, 12, 2735–2744.

    PubMed  CAS  Google Scholar 

  • Liu, Y., Tsinoremas, N. F., Johnson, C. H., Lebedeva, N. V., Golden, S. S., Ishiura, M., & Kondo, T. (1995). Circadian orchestration of gene expression in cyanobacteria. Genes and Development, 9, 1469–1478.

    Article  PubMed  CAS  Google Scholar 

  • Loros, J. J., Denome, S. A., & Dunlap, J. C. (1989). Molecular cloning of genes under control of the circadian clock in Neurospora. Science, 243, 385–388

    Article  Google Scholar 

  • Millar, A. J., Carre, I. A., Strayer, C. A., Chua, N. H., & Kay, S. (1995). Circadian clock mutants in Arabidopsis identified by luciferase imaging. Science, 267, 1161–1163

    Article  PubMed  CAS  Google Scholar 

  • Myers, M. P., Wager-Smith, K., Wesley, C. S., Young, M. W., & Sehgal, A. (1995). Positional cloning and sequence analysis of the Drosophila clock gene, timeless. Science, 270, 805–808.

    Article  PubMed  CAS  Google Scholar 

  • Myers, M. P., Wager-Smith, K., Rothenfluh-Hilfiker, A., &Young, M. W. (1996). Light-induced degradation of Timeless and entrainment of the Drosophila circadian clock. Science, 271, 1736–1740.

    Article  PubMed  CAS  Google Scholar 

  • Nagy, F., Kay, S. A., & Chua, N.-H. (1988). A circadian clock regulates transcription of the wheat Cab-1 gene. Genes and Development, 2, 376–382.

    Article  CAS  Google Scholar 

  • Pierce, M. E., Sheshberadaran, H., Zhang, Z., Fox, L. E., Applebury, M. L., & Takahashi, J. S. (1993). Circadian regulation of iodopsin gene expression in embryonic photoreceptors in retinal cell culture. Neuron, 10, 579–584.

    Article  PubMed  CAS  Google Scholar 

  • Pittendrigh, C. S. (1967). Circadian systems I. The driving oscillation and its assay in Drosophila pseudo-obscura. Proceedings of the National Academy of Sciences of the USA, 58, 1762–1767.

    Article  PubMed  CAS  Google Scholar 

  • Pittendrigh, C. S. (1981). Circadian systems: Entrainment. In J. Aschoff (Ed.), Handbook of Behavioral Neurobiology (pp. 95–124). New York: Plenum Press.

    Google Scholar 

  • Price, J. L., Dembinska, M. E., Young, M. W., & Rosbash, M. (1995). Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless. EMBO Journal, 14, 4044–4047.

    PubMed  CAS  Google Scholar 

  • Ralph, M. R., & Menaker, M. (1988). A mutation of the circadian system in golden hamsters. Science, 241, 1225–1227.

    Article  PubMed  CAS  Google Scholar 

  • Reddy, P., Zehring, W. A., Wheeler, D. A., Pirrota, V., Hadfield, C., Hall, J. C., & Rosbash, M. (1984). Molecular analysis of the period locus of Drosophila melanogaster and identification of a transcript involved in biological rhythms. Cell, 38, 701–710.

    Article  PubMed  CAS  Google Scholar 

  • Reppert, S. M., Tsai, T., Roca, A. L., & Sauman, I. (1994). Cloning of a structural and functional homolog of the circadian clock gene period from the giant silkmoth Antheraea pernyi. Neuron, 13, 1167–1176

    Article  PubMed  CAS  Google Scholar 

  • Reyes, H., Reisz-Porszasa, S., & Hankinson, O. (1992). Identification of the Ah receptor nuclear trans-locator protein (Amt) as a component of the DNA binding form of the Ah receptor. Science, 256, 1193–1195.

    Article  PubMed  CAS  Google Scholar 

  • Rutila, J. E., Zeng, H., Le, M., Curtin, K. D., Hall, J. C., & Rosbash, M. (1996). The timsL mutant of the Drosophila rhythm gene timeless manifests allele-specific interactions with period gene mutants. Neuron, 17, 921–929.

    Article  PubMed  CAS  Google Scholar 

  • Saez, L., & Young, M. W. (1988). In situ localization of the per clock protein during development of Drosophila melanogaster. Mol. Cell. Biol.. 8, 5378–5385.

    PubMed  CAS  Google Scholar 

  • Saez, L., & Young, M. W. (1996). Regulation of nuclear entry of the Drosophila clock proteins Period and Timeless. Neuron 17, 911–920.

    Article  PubMed  CAS  Google Scholar 

  • Sauman, I., & Reppert, S. M. (1996). Circadian clock neurons in the silkmoth Antheraea pernyi: novel mechanisms of period protein regulation. Neuron, 17, 889–900.

    Article  PubMed  CAS  Google Scholar 

  • Sauman, I., Tsai, T., Roca, A. L., & Reppert, S. M. (1996). Period protein is necessary for circadian control of egg hatching behavior in the silkmoth Antheraea pernyi. Neuron 17, 901–909.

    Article  PubMed  CAS  Google Scholar 

  • Saunders, D. S. (1990). The Circadian Basis of Ovarian Diapause regulation in Drosophila melanogaster. Is the period gene causally involved in photoperiodic time measurement? Journal of Biological Rhythms, 5, 315–331.

    Article  PubMed  CAS  Google Scholar 

  • Sehgal, A., Price, J. L., Man, B., and Young, M. W. (1994). Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science, 263, 1603–1606.

    Article  PubMed  CAS  Google Scholar 

  • Sehgal, A., Rothenfluh-Hilfer, A., Hunter-Ensor, M., Chen, Y., Myers, M. P., & Young, M. W. (1995). Rhythmic expression of timeless A basis for promoting circadian cycles in period gene autoreguation. Science, 270, 808–810.

    Article  PubMed  CAS  Google Scholar 

  • Silver, R., LeSauter, J., Tresco, P. A., & Lehman, M. N. (1996). A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature, 382, 810–813.

    Article  PubMed  CAS  Google Scholar 

  • Siwicki, K. K., Eastman, C, Petersen, G., Rosbash, M., & Hall, J. C. (1988). Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron, 1, 141–150.

    Article  PubMed  CAS  Google Scholar 

  • Smith, R. F., & Konopka, R. J. (1982). Effects of dosage alterations at the per locus on the period of the circadian clock of Drosophila. Molecular and General Genetics, 185, 30–36.

    Article  Google Scholar 

  • Takahashi, J. S., & Zatz, M. (1982). Regulation of circadian rhythmicity. Science, 217, 1104–1111.

    Article  PubMed  CAS  Google Scholar 

  • Truman, J. W. (1974). Physiology of insect rhythms IV. Role of the brain in the regulation of the flight rhythm of the giant silkmoth. Journal of Comparative Physiology, 95, 281–296.

    Article  Google Scholar 

  • Van Gelder, R., & Krasnow, M (1996). A novel circadianly expressed Drosophila melanogaster gene dependent on the period gene for its rhythmic expression. EMBO Journal, 15, 1625–1631.

    PubMed  Google Scholar 

  • Van Gelder, R., Bae, H., Palazzolo, M., and Krasnow, M. (1995). Extent and character of circadian gene expression in Drosophila elanogaster. Identification of 20 oscillating mRNAs in the fly head. Current Biology, 5, 1424–1436.

    Article  PubMed  Google Scholar 

  • Vitaterna, M. H., King, D. R, Chang, A.-M., Kornhauser, J. M., Lowrey, R. L., McDonald, J. D., Dove, W. F., Pinto, L. H., Turek, E W., & Takahashi, J. S. (1994). Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science, 264, 719–725.

    Article  PubMed  CAS  Google Scholar 

  • Vosshall L. B., Price, J. L., Sehgal, A., Saez, L., Sc Young, M. W. (1994). Block in nuclear localization of period protein by a second clock mutation, timeless. Science, 263, 1606–1609.

    Article  PubMed  CAS  Google Scholar 

  • Vosshall, L. B., & Young, M. W. (1995). Circadian rhythms in Drosophila can be driven by period expression in a restricted group of central brain cells. Neuron, 15, 345–360.

    Article  PubMed  CAS  Google Scholar 

  • Winfree, A. T. (1970). The temporal morphology of a biological clock. In M. Gerstenhaber (Ed.), Lectures on Mathematics in the Life Sciences (vol.2p. 109). Rhode Island: American Mathematical Society.

    Google Scholar 

  • Young, M. W., & Judd, B. (1978). Nonessential sequences, genes, and the polytene chromosome bands of Drosophila melanogaster. Genetics, 88, 723–742.

    PubMed  CAS  Google Scholar 

  • Young, M. W., Wager-Smith, K., Vosshall, L. B., Saez, L., & Myers, M. P. (1996). Molecular anatomy of a light-sensitive circadian pacemaker in Drosophila. Cold Spring Harbor Symposia on Quantitaive Biology, 61, 279–284.

    Article  CAS  Google Scholar 

  • Yu, Q., Jacquier, A. C., Colot, H. V., Citri, Y., Hamblen, M., Hall, J. C., & Rosbash, M. (1987). Molecular mapping of point mutations in the period gene that stop or speed up biological clocks in Drosophila melanogaster. Proceedings of the National Academy of Sciences of the USA, 84, 784–788.

    Article  PubMed  CAS  Google Scholar 

  • Zehring, W. A., Wheeler, D. A., Reddy, P, Konopka, R. J., Kyriacou, C. P, Rosbash, M., & Hall, J. C. (1984). P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell, 39, 369–376.

    Article  PubMed  CAS  Google Scholar 

  • Zeng, H., Hardin, P. E., & Rosbash, M. (1994). Constitutive overexpression of the Drosophila period protein inhibits period mRNA cycling. EMBO Journal, 13, 3590–3598.

    PubMed  CAS  Google Scholar 

  • Zeng, H., Qian, Z., Myers, M. P., & Rosbash, M. (1996). A light-entrainment mechanism for the Drosophila circadian clock. Nature, 380, 129–135.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Science Foundation Center for Biological Timing, Laboratory of Genetics, The Rockefeller University, New York, New York, 10021

    Michael W. Young

Authors
  1. Michael W. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Northwestern University, Evanston, Illinois, USA

    Joseph S. Takahashi , Fred W. Turek  & Robert Y. Moore ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Young, M.W. (2001). Circadian Timekeeping in Drosophila . In: Takahashi, J.S., Turek, F.W., Moore, R.Y. (eds) Circadian Clocks. Handbook of Behavioral Neurobiology, vol 12. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1201-1_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1201-1_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5438-3

  • Online ISBN: 978-1-4615-1201-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation