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Identification of a Wnt/DVI/β-catenin → Pitx2 Pathway Mediating Cell-Type-Specific Proliferation during Development

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Brault,  Veronique
Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Kemler,  Rolf
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Kioussi, C., Briata, P., Baek, S. H., Rose, D. W., Hamblet, N. S., Herman, T., et al. (2002). Identification of a Wnt/DVI/β-catenin → Pitx2 Pathway Mediating Cell-Type-Specific Proliferation during Development. Cell, 111(5), 673-685.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-95DF-7
Abstract
Understanding the cell type-specific molecular mechanisms by which distinct signaling pathways combinatorially control proliferation during organogenesis is a central issue in development and disease. Here, we report that the bicoid- related transcription factor Pitx2 is rapidly induced by the Wnt/Dvl/β-catenin pathway and is required for effective cell-type-specific proliferation by directly activating specific growth-regulating genes. Regulated exchange of HDACi/β-catenin converts Pitx2 from repressor to activator, analogous to control of TCF/LEFT. Pitx2 then serves as a competence factor required for the temporally ordered and growth factor-dependent recruitment of a series of specific coactivator complexes that prove necessary for Cyclin D2 gene induction. The molecular strategy underlying interactions between the Wnt and growth factor-dependent signaling pathways in cardiac outflow tract and pituitary proliferation is likely to be prototypic of cell-specific proliferation strategies in other tissues.