Probing the canonicity of the Wnt/Wingless signaling pathway

• Published in: PLoS genetics Vol. 13; no. 4; p. e1006700
• Main Authors: Franz, Alexandra, Shlyueva, Daria, Brunner, Erich, Stark, Alexander, Basler, Konrad
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.04.2017; Public Library of Science (PLoS)
• Subjects: Animals; Armadillo Domain Proteins - genetics; Armadillo Domain Proteins - metabolism; Bifurcations; Biology and Life Sciences; Deoxyribonucleic acid; DNA; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Enhancer Elements, Genetic; Fruit flies; Gene Expression Regulation; Gene targeting; Genes; Genetic aspects; Genome, Insect; Genomes; Genomics; Insects; Investigations; Life sciences; Protein binding; Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; Research and Analysis Methods; Sequence Analysis, RNA; Signal Transduction; Somatic chromosomes; Stem cells; Studies; Transcription (Genetics); Transcription Factors - genetics; Transcription Factors - metabolism; Wnt gene; Wnt proteins; Wnt Signaling Pathway; Wnt1 Protein - genetics; Wnt1 Protein - metabolism; β-Catenin
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006700

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.