Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination

Cell. 2006 May 5;125(3):593-605. doi: 10.1016/j.cell.2006.02.046.


While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage / physiology*
  • HeLa Cells
  • Histone Deacetylase 1
  • Histone Deacetylases / metabolism
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Organogenesis / physiology
  • Repressor Proteins / metabolism
  • Signal Transduction / physiology*
  • Transcription Factor Pit-1 / metabolism
  • Transcriptional Activation / physiology
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*


  • Hesx1 protein, mouse
  • Homeodomain Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Pit1 protein, mouse
  • Prophet of Pit-1 protein
  • Repressor Proteins
  • Transcription Factor Pit-1
  • Wnt Proteins
  • beta Catenin
  • Hdac1 protein, mouse
  • Histone Deacetylase 1
  • Histone Deacetylases