Abstract
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.
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References
Hadorn, E. in The Genetics and Biology of Drosophila Vol. 2c (eds Ashburner, M. & Wright, T.) 556–617 (Academic, New York, 1978)
Maves, L. & Schubiger, G. Wingless induces transdetermination in developing Drosophila imaginal discs. Development 121, 1263–1272 (1995)
Sustar, A. & Schubiger, G. A transient cell cycle shift in Drosophila imaginal disc cells precedes multipotency. Cell 120, 383–393 (2005)
Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413–443 (2004)
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)
Shao, Z. et al. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98, 37–46 (1999)
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)
Muller, J. et al. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111, 197–208 (2002)
Cavalli, G. & Paro, R. The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis. Cell 93, 505–518 (1998)
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)
Galko, M. J. & Krasnow, M. A. Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol. 2, E239 (2004)
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)
Zeitlinger, J. & Bohmann, D. Thorax closure in Drosophila: involvement of Fos and the JNK pathway. Development 126, 3947–3956 (1999)
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)
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)
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)
Riesgo-Escovar, J. R. & Hafen, E. Common and distinct roles of DFos and DJun during Drosophila development. Science 278, 669–672 (1997)
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)
Jasper, H. et al. The genomic response of the Drosophila embryo to JNK signalling. Dev. Cell 1, 579–586 (2001)
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)
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)
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)
Maves, L. & Schubiger, G. A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signalling. Development 125, 115–124 (1998)
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)
Okubo, T. & Hogan, B. L. Hyperactive Wnt signalling changes the developmental potential of embryonic lung endoderm. J. Biol. 3, 11 (2004)
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)
Valk-Lingbeek, M. E., Bruggeman, S. W. & van Lohuizen, M. Stem cells and cancer; the Polycomb connection. Cell 118, 409–418 (2004)
Gibson, M. C. & Schubiger, G. Hedgehog is required for activation of engrailed during regeneration of fragmented Drosophila imaginal discs. Development 126, 1591–1599 (1999)
Acknowledgements
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.
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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)
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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). https://doi.org/10.1038/nature04120
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DOI: https://doi.org/10.1038/nature04120
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