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Interactions between Sox9 and beta-catenin control chondrocyte differentiation.

Chondrogenesis is a multistep process that is essential for endochondral bone formation. Previous results have indicated a role for beta-catenin and Wnt signaling in this pathway. Here we show the existence of physical and functional interactions between beta-catenin and Sox9, a transcription factor that is required in successive steps of chondrogenesis. In vivo, either overexpression of Sox9 or inactivation of beta-catenin in chondrocytes of mouse embryos produces a similar phenotype of dwarfism with decreased chondrocyte proliferation, delayed hypertrophic chondrocyte differentiation, and endochondral bone formation. Furthermore, either inactivation of Sox9 or stabilization of beta-catenin in chondrocytes also produces a similar phenotype of severe chondrodysplasia. Sox9 markedly inhibits activation of beta-catenin-dependent promoters and stimulates degradation of beta-catenin by the ubiquitination/proteasome pathway. Likewise, Sox9 inhibits beta-catenin-mediated secondary axis induction in Xenopus embryos. Beta-catenin physically interacts through its Armadillo repeats with the C-terminal transactivation domain of Sox9. We hypothesize that the inhibitory activity of Sox9 is caused by its ability to compete with Tcf/Lef for binding to beta-catenin, followed by degradation of beta-catenin. Our results strongly suggest that chondrogenesis is controlled by interactions between Sox9 and the Wnt/beta-catenin signaling pathway.

Pubmed ID: 15132997


  • Akiyama H
  • Lyons JP
  • Mori-Akiyama Y
  • Yang X
  • Zhang R
  • Zhang Z
  • Deng JM
  • Taketo MM
  • Nakamura T
  • Behringer RR
  • McCrea PD
  • de Crombrugghe B


Genes & development

Publication Data

May 1, 2004

Associated Grants

  • Agency: NICHD NIH HHS, Id: 5T32 HD 07325
  • Agency: NCI NIH HHS, Id: CA 16672
  • Agency: NIAMS NIH HHS, Id: P01 AR 42919

Mesh Terms

  • Animals
  • Binding Sites
  • Cell Differentiation
  • Cell Division
  • Chondrocytes
  • Cyclin D1
  • Cytoskeletal Proteins
  • Enhancer Elements, Genetic
  • Gene Expression
  • Heterozygote
  • High Mobility Group Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Models, Biological
  • Phenotype
  • SOX9 Transcription Factor
  • Signal Transduction
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Xenopus Proteins
  • Xenopus laevis
  • beta Catenin