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Homeodomain-Mediated β-Catenin-Dependent Switching events Dictate Cell-Lineage Determination

By L. Olson, J. Tollkuhn, C. Scafoglio, A. Krones, J. Zhang, K. Ohgi, W. Wu, M. Taketo, R. Kemler, R. Grosschedl, D. Rose and X. Li


While the biological roles of canonical Wnt/β-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 β-catenin remains a major challenge. Here, we report an unexpected strategy for β-catenin-dependent regulation of cell-lineage determination based on interactions between β-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. β-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 coreprossor 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

Year: 2006
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Provided by: MPG.PuRe
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