Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling

Mol Cell. 2009 Dec 11;36(5):872-84. doi: 10.1016/j.molcel.2009.11.017.

Abstract

In response to Wnt stimulation, beta-catenin accumulates and activates target genes. Using modeling and experimental analysis, we found that the level of beta-catenin is sensitive to perturbations in the pathway, such that cellular variation would be expected to alter the signaling outcome. One unusual parameter was robust: the fold-change in beta-catenin level (post-Wnt/pre-Wnt). In Xenopus, dorsal-anterior development and target gene expression are robust to perturbations that alter the final level but leave the fold-change intact. These suggest, first, that despite cellular noise, the cell responds reliably to Wnt stimulation by maintaining a robust fold-change in beta-catenin. Second, the transcriptional machinery downstream of the Wnt pathway does not simply read the beta-catenin level after Wnt stimulation but computes fold-changes in beta-catenin. Analogous to Weber's Law in sensory physiology, some gene transcription networks must respond to fold-changes in signals, rather than absolute levels, which may buffer stochastic, genetic, and environmental variation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Embryo, Nonmammalian / metabolism
  • Humans
  • Models, Theoretical
  • Signal Transduction*
  • Wnt Proteins / metabolism*
  • Xenopus
  • beta Catenin / metabolism*

Substances

  • Wnt Proteins
  • beta Catenin