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Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development
Author(s) -
Smith Nathan,
Dong Yufeng,
Lian Jane B.,
Pratap Jitesh,
Kingsley Paul D.,
van Wijnen Andre J.,
Stein Janet L.,
Schwarz Edward M.,
O'Keefe Regis J.,
Stein Gary S.,
Drissi M. Hicham
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20210
Subject(s) - runx2 , runx1 , biology , chondrocyte , chondrogenesis , transcription factor , cartilage , microbiology and biotechnology , embryonic stem cell , mesenchymal stem cell , genetics , anatomy , gene
Identifying the genetic pathways that regulate skeletal development is necessary to correct a variety of cartilage and bone abnormalities. The Runx family of transcription factors play a fundamental role in organ development and cell differentiation. Initial studies have shown that both Runx1 and Runx2 are expressed in pre‐chondrogenic mesenchyme of the developing embryo at E12.5. Abrogation of the Runx2 gene completely inhibits bone formation yet the cartilage anlagen in these mice is fully formed. In the present study, we hypothesized that Runx1 may compensate for the lack of Runx2 in vivo to induce the early stages of skeletal formation and development. Histologic β‐gal stained sections using the Runx1 +/− ‐Lac‐Z mice demonstrate Runx1 promoter activity in pre‐chondrocytic cell populations. In situ hybridization using Runx1 and Runx2 specific probes indicate that both factors are expressed in mesenchymal stem cell progenitors during early embryonic development. During later stages of mouse skeletal formation, Runx1 is excluded from the hypertrophic cartilage while Runx2 is present in these matured chondrocyte populations. Quantification of Runx expression by real time RT‐PCR and Western blot analyses reveals that Runx1 and Runx2 are differentially modulated during embryogenesis suggesting a temporal role for each of these transcriptional regulators during skeletal formation. We provide evidence that haploinsufficiency results in normal appearing embryo skeletons of heterozygote Runx2 and Runx1 mutant mouse models; however, a delay in bone formation was identified in the calvarium. In summary, our results support a function for Runx1 and Runx2 during skeletal development with a possible role for Runx1 in mediating early events of endochondral and intramembranous bone formation, while Runx2 is a potent inducer of late stages of chondrocyte and osteoblast differentiation. © 2004 Wiley‐Liss, Inc.