Dishevelled limits Notch signalling through inhibition of CSL

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Date

2012-12-01

Author

Collu, Giovanna M.
Hidalgo-Sastre, Ana
Acar, Ahmet
Bayston, Laura
Gildea, Clara
Leverentz, Michael K.
Mills, Christopher G.
Owens, Thomas W.
Meurette, Olivier
Dorey, Karel
Brennan, Keith

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Notch and Wnt are highly conserved signalling pathways that are used repeatedly throughout animal development to generate a diverse array of cell types. However, they often have opposing effects on cell-fate decisions with each pathway promoting an alternate outcome. Commonly, a cell receiving both signals exhibits only Wnt pathway activity. This suggests that Wnt inhibits Notch activity to promote a Wnt-ON/Notch-OFF output; but what might underpin this Notch regulation is not understood. Here, we show that Wnt acts via Dishevelled to inhibit Notch signalling, and that this crosstalk regulates cell-fate specification in vivo during Xenopus development. Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhibitor of Notch signalling and an activator of the Wnt pathway that sharpens the distinction between opposing Wnt and Notch responses, allowing for robust cell-fate decisions.

URI

https://hdl.handle.net/11511/89501

Journal

DEVELOPMENT

DOI

https://doi.org/10.1242/dev.081885

Collections

Department of Biology, Article

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Citation Formats

G. M. Collu et al., “Dishevelled limits Notch signalling through inhibition of CSL,” DEVELOPMENT, pp. 4405–4415, 2012, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/89501.