Probing the canonicity of the Wnt/Wingless signaling pathway

PLoS Genet. 2017 Apr 3;13(4):e1006700. doi: 10.1371/journal.pgen.1006700. eCollection 2017 Apr.

Abstract

The hallmark of canonical Wnt signaling is the transcriptional induction of Wnt target genes by the beta-catenin/TCF complex. Several studies have proposed alternative interaction partners for beta-catenin or TCF, but the relevance of potential bifurcations in the distal Wnt pathway remains unclear. Here we study on a genome-wide scale the requirement for Armadillo (Arm, Drosophila beta-catenin) and Pangolin (Pan, Drosophila TCF) in the Wnt/Wingless(Wg)-induced transcriptional response of Drosophila Kc cells. Using somatic genetics, we demonstrate that both Arm and Pan are absolutely required for mediating activation and repression of target genes. Furthermore, by means of STARR-sequencing we identified Wnt/Wg-responsive enhancer elements and found that all responsive enhancers depend on Pan. Together, our results confirm the dogma of canonical Wnt/Wg signaling and argue against the existence of distal pathway branches in this system.

MeSH terms

  • Animals
  • Armadillo Domain Proteins / genetics
  • Armadillo Domain Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Genome, Insect
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Analysis, RNA
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Wnt Signaling Pathway*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*

Substances

  • ARM protein, Drosophila
  • Armadillo Domain Proteins
  • Drosophila Proteins
  • Repressor Proteins
  • Transcription Factors
  • Wnt1 Protein
  • pan protein, Drosophila
  • wg protein, Drosophila