Loss-of-function of β-catenin bar-1 slows development and activates the Wnt pathway in Caenorhabditis elegans

Sci Rep. 2014 May 13:4:4926. doi: 10.1038/srep04926.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cluster Analysis
  • Collagen / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Variation
  • Hedgehog Proteins / metabolism
  • Male
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcriptome
  • Wnt Signaling Pathway*

Substances

  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • Forkhead Transcription Factors
  • Hedgehog Proteins
  • Transcription Factors
  • bar-1 protein, C elegans
  • daf-16 protein, C elegans
  • Collagen