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

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.
Mesh Terms:
Animals, Cell Differentiation, Cell Lineage, Hela Cells, Histone Deacetylase 1, Histone Deacetylases, Homeodomain Proteins, Humans, Lymphoid Enhancer-Binding Factor 1, Mice, Mice, Knockout, Mice, Transgenic, Organogenesis, Repressor Proteins, Signal Transduction, Transcription Factor Pit-1, Transcriptional Activation, Wnt Proteins, beta Catenin
Cell
Date: May. 05, 2006
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