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

By C. Kioussi, P. Briata, S. Baek, D. Rose, N. Hamblet, T. Herman, K. Ohgi, C. Lin, A. Gleiberman, J. Wang, V. Brault, P. Ruiz-Lozano, H. Nguyen, R. Kemler, C. Glass, A. Wynshaw-Boris and M. Rosenfeld


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

Year: 2002
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Provided by: MPG.PuRe
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