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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.

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

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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.

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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.

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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)

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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

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