Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Division, Cell Line, Cyclin D2, Cyclins, Cytoskeletal Proteins, Gene Expression Regulation, Developmental, Heart, Histone Deacetylases, Homeodomain Proteins, Mice, Mice, Knockout, Mice, Transgenic, Models, Biological, Nuclear Proteins, Organogenesis, Phosphoproteins, Pituitary Gland, Proteins, Proto-Oncogene Proteins, Signal Transduction, Trans-Activators, Transcription Factors, Transcriptional Activation, Wnt Proteins, Zebrafish Proteins, beta Catenin
Cell
Date: Nov. 27, 2002
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