beta-Catenin regulates intercellular signalling networks and cell-type specific transcription in the developing mouse midbrain-rhombomere 1 region

PLoS One. 2010 Jun 3;5(6):e10881. doi: 10.1371/journal.pone.0010881.

Abstract

beta-Catenin is a multifunctional protein involved in both signalling by secreted factors of Wnt family and regulation of the cellular architecture. We show that beta-catenin stabilization in mouse midbrain-rhombomere 1 region leads to robust up-regulation of several Wnt signalling target genes, including Fgf8. Suggestive of direct transcriptional regulation of the Fgf8 gene, beta-catenin stabilization resulted in Fgf8 up-regulation also in other tissues, specifically in the ventral limb ectoderm. Interestingly, stabilization of beta-catenin rapidly caused down-regulation of the expression of Wnt1 itself, suggesting a negative feedback loop. The changes in signal molecule expression were concomitant with deregulation of anterior-posterior and dorso-ventral patterning. The transcriptional regulatory functions of beta-catenin were confirmed by beta-catenin loss-of-function experiments. Temporally controlled inactivation of beta-catenin revealed a cell-autonomous role for beta-catenin in the maintenance of cell-type specific gene expression in the progenitors of midbrain dopaminergic neurons. These results highlight the role of beta-catenin in establishment of neuroectodermal signalling centers, promoting region-specific gene expression and regulation of cell fate determination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Fibroblast Growth Factor 8 / genetics
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Mesencephalon / embryology
  • Mesencephalon / metabolism*
  • Mice
  • Mice, Transgenic
  • Signal Transduction / physiology*
  • Transcription, Genetic / physiology*
  • Wnt1 Protein / genetics
  • beta Catenin / physiology*

Substances

  • Fgf8 protein, mouse
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • beta Catenin
  • Fibroblast Growth Factor 8