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PMID: 15132997 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interactions between Sox9 and beta-catenin control chondrocyte differentiation.

Genes & development ·Vol. 18 ·No. 9 ·2004-05-01 ·Pages 1072-87

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

Abstract

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.

MeSH Terms
Animals Binding Sites Cell Differentiation Cell Division Chondrocytes/cytology,physiology Cyclin D1/metabolism Cytoskeletal Proteins/genetics,physiology Enhancer Elements, Genetic Gene Expression Heterozygote High Mobility Group Proteins/chemistry,genetics,physiology Mice Mice, Inbred C57BL Mice, Mutant Strains Mice, Transgenic Models, Biological Phenotype SOX9 Transcription Factor Signal Transduction Trans-Activators/genetics,physiology Transcription Factors/chemistry,genetics,physiology Transcription, Genetic Xenopus Proteins Xenopus laevis beta Catenin
Chemicals
CTNNB1 protein, Xenopus CTNNB1 protein, mouse Cytoskeletal Proteins High Mobility Group Proteins SOX9 Transcription Factor Sox9 protein, mouse Trans-Activators Transcription Factors Xenopus Proteins beta Catenin Cyclin D1
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Akiyama Haruhiko
Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. hakiyama@mdacc.tmc.edu
Lyons Jon P
Mori-Akiyama Yuko
Yang Xiaohong
Zhang Ren
Zhang Zhaoping
Deng Jian Min
Taketo Makoto M
Nakamura Takashi
Behringer Richard R
McCrea Pierre D
de Crombrugghe Benoit
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1171104
Email
hakiyama@mdacc.tmc.edu
Published
2004-05-01
Pages
1072-87
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC406296
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NICHD NIH HHS · 5T32 HD 07325 · United States
NIGMS NIH HHS · R01 GM052112 · United States
NICHD NIH HHS · T32 HD007325 · United States
NCI NIH HHS · CA 16672 · United States
NIAMS NIH HHS · P01 AR042919 · United States
NIAMS NIH HHS · P01 AR 42919 · United States
External Links
PubMed source DOI: 10.1101/gad.1171104 PMC Full Text View journal details
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