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PMID:12464179
| Citation |
Kioussi, C, Briata, P, Baek, SH, Rose, DW, Hamblet, NS, Herman, T, Ohgi, KA, Lin, C, Gleiberman, A, Wang, J, Brault, V, Ruiz-Lozano, P, Nguyen, HD, Kemler, R, Glass, CK, Wynshaw-Boris, A and Rosenfeld, MG (2002) Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell 111:673-85 |
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| 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/beta-catenin pathway and is required for effective cell-type-specific proliferation by directly activating specific growth-regulating genes. Regulated exchange of HDAC1/beta-catenin converts Pitx2 from repressor to activator, analogous to control of TCF/LEF1. 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. |
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| Keywords |
Adaptor Proteins, Signal Transducing; Animals; Cell Division; Cell Line; Cyclin D2; Cyclins/metabolism; Cytoskeletal Proteins/metabolism; Gene Expression Regulation, Developmental; Heart/embryology; Histone Deacetylases/metabolism; Homeodomain Proteins/metabolism; Mice; Mice, Knockout; Mice, Transgenic; Models, Biological; Nuclear Proteins; Organogenesis/genetics; Phosphoproteins; Pituitary Gland/embryology; Proteins/metabolism; Proto-Oncogene Proteins/metabolism; Signal Transduction; Trans-Activators/metabolism; Transcription Factors/metabolism; Transcriptional Activation; Wnt Proteins; Zebrafish Proteins; beta Catenin |
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Significance
Annotations
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