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Interactions between Sox9 and beta-catenin control chondrocyte differentiation.

Genes & development | May 1, 2004

http://www.ncbi.nlm.nih.gov/pubmed/15132997

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 RIS Download

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

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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

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