Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Imaging of single light-responsive clock cells reveals fluctuating free-running periods

Nature Cell Biology volume 7, pages 319–321 (2005)Cite this article

Abstract

Zebrafish tissues and cell lines contain circadian clocks that respond directly to light1,2. Using fluorescence-activated cell sorting, we have isolated clonal cell lines that contain the reporter construct, zfperiod4-luciferase3. Bioluminescent assays show that oscillations within cell populations are dampened in constant darkness. However, single-cell imaging reveals that individual cells continue to oscillate, but with widely distributed phases and marked stochastic fluctuations in free-running period. Because these cells are directly light responsive, we can easily follow phase shifts to single light pulses. Here we show that light acts to reset desynchronous cellular oscillations to a common phase, as well as stabilize the subsequent free-running period.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Rhythmic oscillations persist within individual cells held in constant conditions.
Figure 2: A light pulse tightens circadian period and resets desynchronized cellular oscillations to a common phase.

Similar content being viewed by others

References

  1. Whitmore, D., Foulkes, N. S., Strahle, U. & Sassone-Corsi, P. Nature Neurosci. 1, 701–707 (1998).

    Article  CAS  Google Scholar 

  2. Whitmore, D., Foulkes, N. S. & Sassone-Corsi, P. Nature 404, 87–91 (2000).

    Article  CAS  Google Scholar 

  3. Vallone, D., Gondi, S. B., Whitmore, D. & Foulkes, N. S. Proc. Natl Acad. Sci. USA. 101, 4106–4111 (2004).

    Article  CAS  Google Scholar 

  4. Plautz, J. D., Kaneko, M., Hall, J. C. & Kay, S. A. Science 278, 1632–1635 (1997).

    Article  CAS  Google Scholar 

  5. Yoo S. H. et al. Proc. Natl Acad. Sci. USA 101, 5339–5346 (2004).

    Article  CAS  Google Scholar 

  6. Nagoshi, E. et al. Cell 119, 693–705 (2004).

    Article  CAS  Google Scholar 

  7. Welsh, D. K., Yoo, S. H., Liu, A. C., Takahashi, J. S. & Kay, S. A. Curr. Biol. 14, 2289–2295 (2004).

    Article  CAS  Google Scholar 

  8. Mihalcescu, I., Hsing, W. & Leibler, S. Nature 430, 81–85 (2004).

    Article  CAS  Google Scholar 

  9. Gonze, D., Halloy, J. & Goldbeter, A. Proc. Natl Acad. Sci. USA. 99, 673–698 (2002).

    Article  CAS  Google Scholar 

  10. Herzog, E. D., Aton, S. T., Numano, R., Sakaki, Y. & Tei, H. J. Biol. Rhythms 19, 35–46 (2004).

    Article  Google Scholar 

  11. Tamai, T. K., Vardhanabhuti, V., Arthur, S., Foulkes, N. S. & Whitmore, D. J. Neuroendocrinol. 15, 344–349 (2003).

    Article  CAS  Google Scholar 

  12. Tamai, T. K., Vardhanabhuti, V., Foulkes, N. S. & Whitmore, D. Curr. Biol. 14, 104–105 (2004).

    Article  Google Scholar 

Download references

Acknowledgements

The authors wish to thank N.S. Foulkes for the kind donation of luciferase reporter cell lines and many useful discussions; K. Allen and D. Davies for their expert assistance with cell sorting; M. Pando for help with retroviral techniques; K. Swann for essential input regarding imaging; J. H. Zhao for advice with circular statistics; M. Straume for guidance with FFT-NLLS; and T. K. Tamai for many useful suggestions. This work was supported by funds from The Wellcome Trust and BBSRC.

Author information

Authors and Affiliations

  1. Department of Anatomy and Developmental Biology, University College London, Centre for Cell and Molecular Dynamics, Rockefeller Building, 21 University Street, London, WC1E 6DE, UK

    Amanda-Jayne F. Carr & David Whitmore

Authors
  1. Amanda-Jayne F. Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Whitmore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Whitmore.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1, S2 and S3 plus movie legends and supplementary methods (PDF 227 kb)

Supplementary Movie 1 (AVI 3472 kb)

Supplementary Movie 2 (AVI 2856 kb)

Supplementary Movie 3 (AVI 4628 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carr, AJ., Whitmore, D. Imaging of single light-responsive clock cells reveals fluctuating free-running periods. Nat Cell Biol 7, 319–321 (2005). https://doi.org/10.1038/ncb1232

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1232

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing