Different Roles of Runx2 During Early Neural Crest-Derived Bone and Tooth Development

Autor: Irma Thesleff, Elina Järvinen, Xiu-Ping Wang, Martyn J. James
Rok vydání: 2006
Předmět:
musculoskeletal diseases
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Mesenchyme
Core Binding Factor Alpha 1 Subunit
Cell Communication
In situ hybridization
Biology
Fibroblast growth factor
Bone tissue
Mesoderm
Mice
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Internal medicine
medicine
Animals
Orthopedics and Sports Medicine
Oligonucleotide Array Sequence Analysis
030304 developmental biology
0303 health sciences
Bone Development
Gene Expression Profiling
musculoskeletal
neural
and ocular physiology
Gene Expression Regulation
Developmental
Neural crest
Epithelial Cells
Osteoblast
Mice
Mutant Strains
Cell biology
medicine.anatomical_structure
Endocrinology
Neural Crest
embryonic structures
Intramembranous ossification
BAMBI
Tooth
030217 neurology & neurosurgery
Zdroj: Journal of Bone and Mineral Research. 21:1034-1044
ISSN: 0884-0431
DOI: 10.1359/jbmr.060413
Popis: We compared gene expression profiles between Runx2 null mutant mice and their wildtype littermates. Most Runx2-dependent genes in bones were different from those in teeth, implying that the target genes of Runx2 are tissue-dependent. In vitro experiments determined that Runx2 is a part of the FGF and BMP signaling pathways in tooth and bone development, respectively. Introduction:Runx2 (Cbfa1) is expressed in the neural crest–derived mesenchyme of developing bone and tooth. Runx2 homozygous null mice lack bone through a failure in osteoblast differentiation and have arrested tooth development at the late bud stage. The aim of this study was to discover and compare the identities and the roles of Runx2 target genes in bone and tooth development. Materials and Methods: Wildtype and Runx2−/− tissue was collected from mouse embryos, and gene expression was compared by Affymetrix microarray analysis and radioactive in situ hybridization of embryonic tissue sections (E12–E14). Induction of target genes by growth factors in bone and tooth tissue was studied using in vitro experiments, including a novel method involving hanging-drop cultures and RT-PCR. Results: Thirteen bone and four tooth genes were identified that are Runx2-dependent. The identities of these genes do not significantly overlap between bone and tooth, indicating tissue specificity of several genes regulated by Runx2. Genes downregulated in bone development in Runx2 null mutants were Bambi, Bmp4, Bono1, Dkk1, Fgf receptor1, Gli1, Lef1, Patched, Prostaglandin F receptor1, Tcf1, Tgfβ1, Wnt10a, and Wnt10b. Several of these genes were induced by BMPs in bone tissue in a Runx2-independent manner. Genes downregulated in tooth development were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast growth factors (FGFs) in dental tissue. FGF-induction of Dkk1 was completely dependent on Runx2 function. Conclusions: The contrasting identities and distinctive mechanisms that stimulate the expression of Runx2-dependent genes in bone and tooth development imply that the developmental roles of Runx2 in these separate tissues are different. In tooth development, Dkk1 may be a direct transcriptional target of Runx2. Bone genes were stimulated by BMP4 before the formation of the ossification center, suggesting that BMPs may mediate the early epithelial–mesenchymal interactions involved in bone formation.
Databáze: OpenAIRE
Externí odkaz: