Identification of a Wnt/Dvl/β-catenin → Pitx2 pathway mediating cell-type-specific proliferation during development

Chrissa Kioussi, Paola Briata, Sung Hee Baek, David W. Rose, Natasha S. Hamblet, Thomas Herman, Kenneth A. Ohgi, Chijen Lin, Anatoli Gleiberman, Jianbo Wang, Veronique Brault, Pilar Ruiz-Lozano, H. D. Nguyen, Rolf Kemler, Christopher K. Glass, Anthony Wynshaw-Boris, Michael G. Rosenfeld

Research output: Contribution to journalArticle

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 HDAC1/β-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.

Original languageEnglish
Pages (from-to)673-685
Number of pages13
JournalCell
Volume111
Issue number5
DOIs
Publication statusPublished - Nov 27 2002

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Kioussi, C., Briata, P., Baek, S. H., Rose, D. W., Hamblet, N. S., Herman, T., Ohgi, K. A., Lin, C., Gleiberman, A., Wang, J., Brault, V., Ruiz-Lozano, P., Nguyen, H. D., Kemler, R., Glass, C. K., Wynshaw-Boris, A., & Rosenfeld, M. G. (2002). Identification of a Wnt/Dvl/β-catenin → Pitx2 pathway mediating cell-type-specific proliferation during development. Cell, 111(5), 673-685. https://doi.org/10.1016/S0092-8674(02)01084-X