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Probing the canonicity of the Wnt/Wingless signaling pathway

Alexandra Franz1, Daria Shlyueva2, Erich Brunner1

  • 1Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Plos Genetics
|April 4, 2017
PubMed

Insights

This study confirms that beta-catenin (Arm) and TCF (Pan) are essential for Wnt/Wingless signaling in Drosophila cells. The findings support the canonical Wnt pathway model and rule out alternative signaling branches.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Canonical Wnt signaling involves beta-catenin/TCF complex driving gene transcription.
  • The existence of alternative Wnt pathway branches remains uncertain.
  • Drosophila melanogaster serves as a model organism to study conserved biological pathways.

Purpose of the Study:

  • To investigate the genome-wide requirement of Armadillo (Arm) and Pangolin (Pan) in Wnt/Wingless (Wg) signaling.
  • To determine the role of Arm and Pan in Wnt/Wg-induced transcriptional responses in Drosophila Kc cells.
  • To assess the relevance of potential bifurcations in the distal Wnt pathway.

Main Methods:

  • Genome-wide analysis using somatic genetics in Drosophila Kc cells.
  • STARR-sequencing to identify Wnt/Wg-responsive enhancer elements.
  • Functional assays to assess the role of Arm and Pan in gene regulation.

Main Results:

  • Armadillo (Arm) and Pangolin (Pan) are indispensable for both activation and repression of Wnt/Wg target genes.
  • All identified Wnt/Wg-responsive enhancers require Pan for their function.
  • No evidence for distal pathway branches was found in this system.

Conclusions:

  • The study validates the canonical Wnt/Wg signaling pathway as the primary mechanism for transcriptional response.
  • Results strongly argue against the existence of alternative distal Wnt pathway branches in Drosophila Kc cells.
  • This work reinforces the central role of the beta-catenin/TCF complex in Wnt signaling.

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