title: Probing the canonicity of the Wnt/Wingless signaling pathway.
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.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Franz
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, Vienna, Austria.
authors.forename: Daria
authors.identifier: 0000-0002-8990-0843
authors.initials: D
authors.lastname: Shlyueva
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Brunner
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Basler
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D049750:Genome, Insect; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C115159:pan protein, Drosophila; C074622:wg protein, Drosophila