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:

Small-molecule regulation of zebrafish gene expression

Abstract

The zebrafish has emerged as a versatile model organism for biomedical research, yet its potential has been limited by a lack of conditional reverse-genetic tools. Here we report a chemically inducible gene expression technology that has orthogonality to vertebrate signaling processes, high induction levels, and rapid kinetics. Coupled with tissue-specific promoters, this system provides multidimensional control of gene expression and will enable new models of human disorders and diseases.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: A chemically inducible gene expression system for zebrafish.
Figure 2: GV-EcR transactivators permit rapid spatiotemporal control of gene expression.

Similar content being viewed by others

References

  1. Adam, A., Bartfai, R., Lele, Z., Krone, P.H. & Orban, L. Exp. Cell Res. 256, 282–290 (2000).

    Article  CAS  Google Scholar 

  2. de Graaf, M., Zivkovic, D. & Joore, J. Dev. Growth Differ. 40, 577–582 (1998).

    Article  CAS  Google Scholar 

  3. Huang, C.J. et al. Dev. Dyn. 233, 1294–1303 (2005).

    Article  CAS  Google Scholar 

  4. No, D., Yao, T.P. & Evans, R.M. Proc. Natl. Acad. Sci. USA 93, 3346–3351 (1996).

    Article  CAS  Google Scholar 

  5. Sawada, Y. et al. Pest Manag. Sci. 59, 25–35 (2003).

    Article  CAS  Google Scholar 

  6. Shimizu, B. et al. Steroids 62, 638–642 (1997).

    Article  CAS  Google Scholar 

  7. Yao, T.P. et al. Nature 366, 476–479 (1993).

    Article  CAS  Google Scholar 

  8. Padidam, M., Gore, M., Lu, D.L. & Smirnova, O. Transgenic Res. 12, 101–109 (2003).

    Article  CAS  Google Scholar 

  9. Karzenowski, D., Potter, D.W. & Padidam, M. Biotechniques 39, 191–200 (2005).

    Article  CAS  Google Scholar 

  10. Huang, C.J., Tu, C.T., Hsiao, C.D., Hsieh, F.J. & Tsai, H.J. Dev. Dyn. 228, 30–40 (2003).

    Article  CAS  Google Scholar 

  11. Xu, Y. et al. DNA Cell Biol. 18, 85–95 (1999).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Fujiwara (University of Tokyo; B. mori EcR complementary DNA), K. Iatrou (National Centre for Scientific Research 'Demokritos' B. mori EcR complementary DNA), J. Knez (McMaster University; pSPUTK-VP16), D. Jongejan-Zivkovic (Hubrecht Laboratory; pUAS:Luc/pG4TLuc and pG4TEX), D. Stainier (University of California, San Francisco; pGIX) and G. Burns (Harvard-Massachusetts General Hospital; myl7 promoter) for providing plasmids. This work was supported by the US National Institutes of Health/National Institute of General Medical Sciences (R01 GM072600) and a Basil O'Connor Starter Scholar Research Award from the March of Dimes Foundation.

Author information

Authors and Affiliations

Authors

Contributions

H.E., V.C. and J.K.C. designed and experimentally evaluated the GV-EcR system; J.K.M. synthesized the nonsteroidal EcR agonists; and J.K.C. conceived the project and prepared the manuscript.

Corresponding author

Correspondence to James K Chen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

GV-EcR and agonist activities in zebrafish and tissue culture. (PDF 3199 kb)

Supplementary Fig. 2

Structural optimization of GV-EcR transactivator/ligand interactions. (PDF 628 kb)

Supplementary Fig. 3

Kinetics of ligand-dependent GV-EcR translocation. (PDF 1569 kb)

Supplementary Fig. 4

Statistical analysis of tebufenozide-dependent, tissue-specific GFP expression in zebrafish embryos. (PDF 2442 kb)

Supplementary Methods (PDF 207 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esengil, H., Chang, V., Mich, J. et al. Small-molecule regulation of zebrafish gene expression. Nat Chem Biol 3, 154–155 (2007). https://doi.org/10.1038/nchembio858

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio858

This article is cited by

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