title: Loss-of-function of β-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans.
abstract: C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
authors.affiliation: 1] Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands [2].
authors.forename: M Leontien
authors.initials: ML
authors.lastname: van der Bent
authors.affiliation: 1] Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands [2].
authors.forename: Mark G
authors.initials: MG
authors.lastname: Sterken
authors.affiliation: 1] Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands [2].
authors.forename: Rita J M
authors.initials: RJ
authors.lastname: Volkers
authors.affiliation: Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: Joost A G
authors.initials: JA
authors.lastname: Riksen
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmid
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Hajnal
authors.affiliation: Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Kammenga
authors.affiliation: Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: L Basten
authors.initials: LB
authors.lastname: Snoek
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D003094:Collagen / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D014644:Genetic Variation; D053823:Hedgehog Proteins / Q000378:metabolism; D008297:Male; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D060449:Wnt Signaling Pathway
chemical_list: D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D051858:Forkhead Transcription Factors; D053823:Hedgehog Proteins; D014157:Transcription Factors; C115014:bar-1 protein, C elegans; C108831:daf-16 protein, C elegans; D003094:Collagen