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

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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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.

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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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Correspondence to Renato Paro.

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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)

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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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