Microarray analysis on Runx2-deficient mouse embryos reveals novel Runx2 functions and target genes during intramembranous and endochondral bone formation

B.L.T. Vaes, P. Ducy, A.M. Sijbers, J.M.A. Hendriks, E.P. van Someren, N.G. de Jong, E.R. van den Heuvel, W. Olijve, E.J.J. van Zoelen, K.J. Dechering

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Abstract

A major challenge in developmental biology is to correlate genome-wide gene expression modulations with developmental processes in vivo. In this study, we analyzed the role of Runx2 during intramembranous and endochondral bone development, by comparing gene expression profiles in 14.5 dpc wild-type and Runx2 (¿/¿) mice. A total of 1277, 606 and 492 transcripts were found to be significantly modulated by Runx2 in calvaria, forelimbs and hindlimbs, respectively. Bioinformatics analysis indicated that Runx2 not only controls the processes of osteoblast differentiation and chondrocyte maturation, but may also play a role in axon formation and hematopoietic cell commitment during bone development. A total of 41 genes are affected by the Runx2 deletion in both intramembranous and endochondral bone, indicating common pathways between these two developmental modes of bone formation. In addition, we identified genes that are specifically involved in endochondral ossification. In conclusion, our data show that a comparative genome-wide expression analysis of wild-type and mutant mouse models allows the examination of mutant phenotypes in complex tissues
Original languageEnglish
Pages (from-to)724-738
JournalBone
Volume39
Issue number4
DOIs
Publication statusPublished - 2006

Keywords

  • stem-cell factor
  • transcription factor runx2
  • sympathetic-nervous-system
  • in-situ hybridization
  • osteoblast differentiation
  • chondrocyte differentiation
  • mast-cells
  • osteogenic differentiation
  • sialoprotein promoter
  • cbfa1-deficient mice

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    Vaes, B. L. T., Ducy, P., Sijbers, A. M., Hendriks, J. M. A., van Someren, E. P., de Jong, N. G., ... Dechering, K. J. (2006). Microarray analysis on Runx2-deficient mouse embryos reveals novel Runx2 functions and target genes during intramembranous and endochondral bone formation. Bone, 39(4), 724-738. https://doi.org/10.1016/j.bone.2006.04.024