Probing the canonicity of the Wnt/Wingless signaling pathway

Alexandra Franz; Daria Shlyueva; Erich Brunner; Alexander Stark; Konrad Basler

doi:10.1371/journal.pgen.1006700

Probing the canonicity of the Wnt/Wingless signaling pathway

Alexandra Franz, Daria Shlyueva, Erich Brunner, Alexander Stark, Konrad Basler

20 Citations (Scopus)

18 Downloads (Pure)

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.

Original language	English
Article number	e1006700
Journal	PLOS Genetics
Volume	13
Issue number	4
Number of pages	18
ISSN	1553-7390
DOIs	https://doi.org/10.1371/journal.pgen.1006700
Publication status	Published - 1 Apr 2017
Externally published	Yes

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Probing the canonicity of the Wnt/Wingless signaling pathwayFinal published version, 2.16 MBLicence: CC BY

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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.",

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AU - Franz, Alexandra

AU - Shlyueva, Daria

AU - Brunner, Erich

AU - Stark, Alexander

AU - Basler, Konrad

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AB - 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.

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Probing the canonicity of the Wnt/Wingless signaling pathway

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