Skip to main content

Thank you for visiting 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.

Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs


During the regeneration of Drosophila imaginal discs, cellular identities can switch fate in a process known as transdetermination1. For leg-to-wing transdetermination, the underlying mechanism involves morphogens such as Wingless that, when activated outside their normal context, induce ectopic expression of the wing-specific selector gene vestigial2,3. Polycomb group (PcG) proteins maintain cellular fates by controlling the expression patterns of homeotic genes and other developmental regulators4. Here we report that transdetermination events are coupled to PcG regulation. We show that the frequency of transdetermination is enhanced in PcG mutant flies. Downregulation of PcG function, as monitored by the reactivation of a silent PcG-regulated reporter gene, is observed in transdetermined cells. This downregulation is directly controlled by theJun amino-terminal kinase (JNK) signalling pathway, which is activated in cells undergoing regeneration. Accordingly, transdetermination frequency is reduced in a JNK mutant background. This regulatory interaction also occurs in mammalian cells, indicating that the role of this signalling cascade in remodelling cellular fates may be conserved.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: PcG genes control transdetermination events.
Figure 2: JNK signalling is activated at the fragmentation site.
Figure 3: Activation of JNK leads to downregulation of PcG genes.
Figure 4: Impaired JNK signalling reduces the transdetermination ratio.


  1. Hadorn, E. in The Genetics and Biology of Drosophila Vol. 2c (eds Ashburner, M. & Wright, T.) 556–617 (Academic, New York, 1978)

    Google Scholar 

  2. Maves, L. & Schubiger, G. Wingless induces transdetermination in developing Drosophila imaginal discs. Development 121, 1263–1272 (1995)

    CAS  PubMed  Google Scholar 

  3. Sustar, A. & Schubiger, G. A transient cell cycle shift in Drosophila imaginal disc cells precedes multipotency. Cell 120, 383–393 (2005)

    CAS  Article  Google Scholar 

  4. Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413–443 (2004)

    CAS  Article  Google Scholar 

  5. Otte, A. P. & Kwaks, T. H. Gene repression by Polycomb group protein complexes: a distinct complex for every occasion? Curr. Opin. Genet. Dev. 13, 448–454 (2003)

    CAS  Article  Google Scholar 

  6. Shao, Z. et al. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98, 37–46 (1999)

    CAS  Article  Google Scholar 

  7. Czermin, B. et al. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111, 185–196 (2002)

    CAS  Article  Google Scholar 

  8. Muller, J. et al. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111, 197–208 (2002)

    CAS  Article  Google Scholar 

  9. Cavalli, G. & Paro, R. The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis. Cell 93, 505–518 (1998)

    CAS  Article  Google Scholar 

  10. Ramet, M., Lanot, R., Zachary, D. & Manfruelli, P. JNK signalling pathway is required for efficient wound healing in Drosophila. Dev. Biol. 241, 145–156 (2002)

    Article  Google Scholar 

  11. Galko, M. J. & Krasnow, M. A. Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol. 2, E239 (2004)

    Article  Google Scholar 

  12. Bosch, M., Serras, F., Martin-Blanco, E. & Baguna, J. JNK signalling pathway required for wound healing in regenerating Drosophila wing imaginal discs. Dev. Biol. 280, 73–86 (2005)

    CAS  Article  Google Scholar 

  13. Zeitlinger, J. & Bohmann, D. Thorax closure in Drosophila: involvement of Fos and the JNK pathway. Development 126, 3947–3956 (1999)

    CAS  PubMed  Google Scholar 

  14. Glise, B., Bourbon, H. & Noselli, S. hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial cell sheet movement. Cell 83, 451–461 (1995)

    CAS  Article  Google Scholar 

  15. Riesgo-Escovar, J. R., Jenni, M., Fritz, A. & Hafen, E. The Drosophila Jun-N-terminal kinase is required for cell morphogenesis but not for DJun-dependent cell fate specification in the eye. Genes Dev. 10, 2759–2768 (1996)

    CAS  Article  Google Scholar 

  16. Perkins, K., Dailey, G. & Tjian, R. Novel Jun- and Fos-related proteins in Drosophila are functionally homologous to enhancer factor AP-1. EMBO J. 7, 4265–4273 (1988)

    CAS  Article  Google Scholar 

  17. Riesgo-Escovar, J. R. & Hafen, E. Common and distinct roles of DFos and DJun during Drosophila development. Science 278, 669–672 (1997)

    ADS  CAS  Article  Google Scholar 

  18. Martin-Blanco, E. et al. puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev. 12, 557–570 (1998)

    CAS  Article  Google Scholar 

  19. Jasper, H. et al. The genomic response of the Drosophila embryo to JNK signalling. Dev. Cell 1, 579–586 (2001)

    CAS  Article  Google Scholar 

  20. Weber, U., Paricio, N. & Mlodzik, M. Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye. Development 127, 3619–3629 (2000)

    CAS  PubMed  Google Scholar 

  21. Shaulian, E. et al. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell 103, 897–907 (2000)

    CAS  Article  Google Scholar 

  22. Bonny, C., Oberson, A., Negri, S., Sauser, C. & Schorderet, D. F. Cell-permeable peptide inhibitors of JNK: novel blockers of β-cell death. Diabetes 50, 77–82 (2001)

    CAS  Article  Google Scholar 

  23. Maves, L. & Schubiger, G. A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signalling. Development 125, 115–124 (1998)

    CAS  PubMed  Google Scholar 

  24. Maves, L. & Schubiger, G. Transdetermination in Drosophila imaginal discs: a model for understanding pluripotency and selector gene maintenance. Curr. Opin. Genet. Dev. 13, 472–479 (2003)

    CAS  Article  Google Scholar 

  25. Okubo, T. & Hogan, B. L. Hyperactive Wnt signalling changes the developmental potential of embryonic lung endoderm. J. Biol. 3, 11 (2004)

    Article  Google Scholar 

  26. Ringrose, L., Rehmsmeier, M., Dura, J. M. & Paro, R. Genome-wide prediction of Polycomb/Trithorax response elements in Drosophila melanogaster. Dev. Cell 5, 759–771 (2003)

    CAS  Article  Google Scholar 

  27. Valk-Lingbeek, M. E., Bruggeman, S. W. & van Lohuizen, M. Stem cells and cancer; the Polycomb connection. Cell 118, 409–418 (2004)

    CAS  Article  Google Scholar 

  28. Gibson, M. C. & Schubiger, G. Hedgehog is required for activation of engrailed during regeneration of fragmented Drosophila imaginal discs. Development 126, 1591–1599 (1999)

    CAS  PubMed  Google Scholar 

Download references


We thank W. Gehring for teaching us the transplantation technique; G. Schubiger for advice; D. Bohmann for the anti-Fos antibody and fly lines; S. B. Carroll for the anti-Vg antibody; K. Basler, S. Noselli, S. Cohen, J. Grosshans and the Tübingen Fly Stock Collection for fly lines; S. Dlugosz and F. Zimmermann for technical support with injection needles; O. Pein and P. Angel for mouse embryonic fibroblast cells and advice; C. Beisel, S. Schönfelder and M. Tariq for comments and discussions. R.P. was funded by the Deutsche Forschungsgemeinschaft.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Renato Paro.

Ethics declarations

Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Methods and Supplementary Figure Legends (DOC 24 kb)

Supplementary Figure 1

LW-1 discs show no re-activation of β-galactosidase upon fragmentation. (PDF 673 kb)

Supplementary Figure 2

vestigial and wingless possess PREs. (PDF 768 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lee, N., Maurange, C., Ringrose, L. et al. Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs. Nature 438, 234–237 (2005).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


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