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Runx2 protein represses Axin2 expression in osteoblasts and is required for craniosynostosis in Axin2-deficient mice

Meghan E McGee-Lawrence1, Xiaodong Li, Krista L Bledsoe

  • 1Mayo Clinic, Rochester, Minnesota 55905, USA.

The Journal of Biological Chemistry
|January 10, 2013
PubMed

Insights

Runx2 and Hdac3 suppress Axin2 to prevent premature skull suture fusion during craniofacial development. Runx2 haploinsufficiency rescues craniosynostosis in Axin2-deficient mice, revealing a key regulatory pathway.

Area of Science:

  • Genetics and Developmental Biology
  • Molecular Biology
  • Skeletal Biology

Background:

  • Runx2 is crucial for calvarial bone development; its deficiency causes cleidocranial dysplasia.
  • Axin2 deficiency leads to craniosynostosis due to elevated beta-catenin activity.
  • Runx2 represses Axin2 transcription, suggesting an in vivo regulatory relationship.

Purpose of the Study:

  • To investigate the mechanistic link between Runx2 and Axin2 in craniofacial development.
  • To determine if Runx2 influences the craniosynostosis phenotype observed in Axin2 deficiency.
  • To elucidate the role of Hdac3 in Runx2-mediated Axin2 regulation.

Main Methods:

  • Analysis of Runx2 binding to the Axin2 promoter.
  • Assessment of Runx2-mediated repression of Axin2 transcription involving Hdac3.
  • Generation and phenotypic analysis of Axin2(-/-):Runx2(+/-) double mutant mice.

Main Results:

  • Runx2 directly binds to multiple regions of the Axin2 promoter.
  • Runx2-dependent repression of Axin2 transcription requires Hdac3.
  • Runx2 haploinsufficiency partially rescued the craniosynostosis phenotype in Axin2-deficient mice, resulting in longer skulls.

Conclusions:

  • Runx2, via Hdac3, suppresses Axin2 transcription, preventing premature calvarial suture closure.
  • This Runx2-Hdac3-Axin2 pathway is critical for regulating intramembranous bone development in the skull.
  • Understanding this mechanism offers insights into craniofacial development and related disorders.

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