Dishevelled limits Notch signalling through inhibition of CSL

Giovanna M Collu1, Ana Hidalgo-Sastre, Ahmet Acar

  • 1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. giovanna.collu@mssm.edu

Development (Cambridge, England)
|November 8, 2012
PubMed

Insights

Wnt signaling inhibits Notch signaling through Dishevelled, which directly blocks CSL transcription factors. This crosstalk ensures robust cell-fate decisions during development.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Signaling

Background:

  • Notch and Wnt are conserved signaling pathways crucial for animal development.
  • These pathways often have opposing roles in cell-fate determination.
  • Wnt signaling typically dominates when both pathways are active, suggesting Wnt inhibits Notch, but the mechanism is unknown.

Purpose of the Study:

  • To elucidate the molecular mechanism by which Wnt signaling inhibits Notch signaling.
  • To investigate the role of this crosstalk in cell-fate specification during Xenopus development.
  • To identify the key molecules involved in mediating Wnt-induced Notch inhibition.

Main Methods:

  • Utilized Xenopus laevis as an in vivo model system.
  • Investigated protein-protein interactions between Wnt pathway components and Notch signaling effectors.
  • Assessed the impact of Dishevelled on CSL transcription factor activity downstream of Notch receptors.

Main Results:

  • Demonstrated that Wnt signaling inhibits Notch signaling via Dishevelled.
  • Showed that Dishevelled directly binds to and inhibits CSL transcription factors.
  • Confirmed that this Wnt-Dishevelled-CSL interaction regulates cell-fate specification in vivo.
  • Provided evidence for the conservation of this crosstalk mechanism across species.

Conclusions:

  • Discovered a novel mechanism where Dishevelled acts as a direct inhibitor of Notch signaling by targeting CSL transcription factors.
  • Identified a dual role for Dishevelled in activating Wnt and inhibiting Notch signaling.
  • Established that this crosstalk sharpens opposing pathway responses, enabling robust cell-fate decisions.

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