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Dkk1 Controls Cell-Cell Interaction through Regulation of Non-nuclear β-Catenin Pools

Marie Johansson1, Florence A Giger1, Triona Fielding1

  • 1Centre for Developmental Neurobiology and MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK.

Developmental Cell
|December 2, 2019
PubMed

Insights

Dickkopf-1 (Dkk1) regulates cell adhesion and polarity during zebrafish development. This secreted Wnt antagonist controls cell connectivity and β-catenin localization, impacting cell migration.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Dickkopf-1 (Dkk1) is a secreted Wnt antagonist crucial for embryonic head development.
  • Emerging evidence suggests Dkk1's involvement in malignancies and neurodegenerative diseases via unelucidated mechanisms.
  • Understanding Dkk1's non-canonical functions is vital for disease research.

Purpose of the Study:

  • To elucidate the mechanism of Dickkopf-1 (Dkk1) in regulating collective cell migration.
  • To investigate Dkk1's role in cell connectivity and polarity independent of its Wnt antagonism.
  • To explore Dkk1's direct involvement in cell adhesion regulation.

Main Methods:

  • Utilizing zebrafish gastrulation as a model for in vivo collective cell migration.
  • Analyzing Dkk1 localization at adhesion complexes and actomyosin regions.
  • Assessing the impact of Dkk1 on cell polarization and β-catenin distribution.

Main Results:

  • Dkk1 localizes to plasma membrane adhesion complexes and actomyosin regions.
  • Dkk1 represses cell polarization and cell-cell adhesion integrity, independent of β-catenin degradation.
  • Dkk1 restricts β-catenin to a submembrane pool, preventing its nuclear localization.

Conclusions:

  • Dkk1 directly regulates cell adhesion and polarity during zebrafish gastrulation.
  • Dkk1's novel mechanism involves controlling β-catenin distribution, not solely degradation.
  • This mechanism impacts both cell adhesion and Wnt/β-catenin transcriptional output.
Keywords:
Dickkopf-1Dkk1Wnt signaling morphogenesiscell adhesioncell migrationmetastasisneurodegenerationpolarityβ-catenin

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