title: Microarray analysis on Runx2-deficient mouse embryos reveals novel Runx2 functions and target genes during intramembranous and endochondral bone formation.
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.
authors.affiliation: Department of Applied Biology FNWI, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
authors.forename: Bart L T
authors.initials: BL
authors.lastname: Vaes
authors.forename: Patricia
authors.initials: P
authors.lastname: Ducy
authors.forename: Anneke M
authors.initials: AM
authors.lastname: Sijbers
authors.forename: José M A
authors.initials: JM
authors.lastname: Hendriks
authors.forename: Eugene P
authors.initials: EP
authors.lastname: van Someren
authors.forename: Nanning G
authors.initials: NG
authors.lastname: de Jong
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.forename: Wiebe
authors.initials: W
authors.lastname: Olijve
authors.forename: Everardus J J
authors.initials: EJ
authors.lastname: van Zoelen
authors.forename: Koen J
authors.initials: KJ
authors.lastname: Dechering
mesh_terms: D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000502:physiology; D005260:Female; D005552:Forelimb / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006614:Hindlimb / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010012:Osteogenesis / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000196:embryology / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse