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

Academic Article

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.
  • Published In

  • Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Kioussi C; Briata P; Baek SH; Rose DW; Hamblet NS; Herman T; Ohgi KA; Lin C; Gleiberman A; Wang J
  • Start Page

  • 673
  • End Page

  • 685
  • Volume

  • 111
  • Issue

  • 5