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

• Published in: Bone (New York, N.Y.) Vol. 39; no. 4; pp. 724 - 738
• Main Authors: Vaes, Bart L.T., Ducy, Patricia, Sijbers, Anneke M., Hendriks, José M.A., van Someren, Eugene P., de Jong, Nanning G., van den Heuvel, Edwin R., Olijve, Wiebe, van Zoelen, Everardus J.J., Dechering, Koen J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2006; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Bone; cbfa1-deficient mice; chondrocyte differentiation; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - physiology; Development; Female; Forelimb - embryology; Forelimb - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Hindlimb - embryology; Hindlimb - metabolism; in-situ hybridization; Male; mast-cells; Mice; Mice, Knockout; Microarray; Mouse; Mutation - genetics; Oligonucleotide Array Sequence Analysis - methods; osteoblast differentiation; Osteogenesis - genetics; Osteogenesis - physiology; osteogenic differentiation; Reverse Transcriptase Polymerase Chain Reaction; Runx2; sialoprotein promoter; Skull - embryology; Skull - metabolism; stem-cell factor; sympathetic-nervous-system; transcription factor runx2; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Development; Bone; Mouse; Microarray; Runx2; Vertebrata; Embryo; Mammalia; Animal; Morphology; Rodentia
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2006.04.024

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.