Runx1 and runx2 cooperate during sternal morphogenesis

Ayako Kimura, Hiroyuki Inose, Fumiko Yano, Koji Fujita, Toshiyuki Ikeda, Shingo Sato, Makiko Iwasaki, Tetsuya Jinno, Keisuke Ae, Seiji Fukumoto, Yasuhiro Takeuchi, Hiroshi Itoh, Takeshi Imamura, Hiroshi Kawaguchi, Ung Il Chung, James F. Martin, Sachiko Iseki, Ken Ichi Shinomiya, Shu Takeda

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Chondrocyte differentiation is strictly regulated by various transcription factors, including Runx2 and Runx3; however, the physiological role of Runx1 in chondrocyte differentiation remains unknown. To examine the role of Runx1, we generated mesenchymal-cell-specific and chondrocyte-specific Runx1-deficient mice [Prx1 Runx1f/f mice and α1(II) Runx1f/f mice, respectively] to circumvent the embryonic lethality of Runx1-deficient mice. We then mated these mice with Runx2 mutant mice to obtain mesenchymal-cell-specific or chondrocyte-specific Runx1; Runx2 double-mutant mice [Prx1 DKO mice and α1(II) DKO mice, respectively]. Prx1 Runx1f/f mice displayed a delay in sternal development and Prx1 DKO mice completely lacked a sternum. By contrast, α1(II) Runx1f/f mice and α1(II) DKO mice did not show any abnormal sternal morphogenesis or chondrocyte differentiation. Notably, Runx1, Runx2 and the Prx1-Cre transgene were co-expressed specifically in the sternum, which explains the observation that the abnormalities were limited to the sternum. Histologically, mesenchymal cells condensed normally in the prospective sternum of Prx1 DKO mice; however, commitment to the chondrocyte lineage, which follows mesenchymal condensation, was significantly impaired. In situ hybridization analyses demonstrated that the expression of α1(II) collagen (Col2a1 - Mouse Genome Informatics), Sox5 and Sox6 in the prospective sternum of Prx1 DKO mice was severely attenuated, whereas Sox9 expression was unchanged. Molecular analyses revealed that Runx1 and Runx2 induce the expression of Sox5 and Sox6, which leads to the induction of α1(II) collagen expression via the direct regulation of promoter activity. Collectively, these results show that Runx1 and Runx2 cooperatively regulate sternal morphogenesis and the commitment of mesenchymal cells to become chondrocytes through the induction of Sox5 and Sox6.

Original languageEnglish
Pages (from-to)1159-1167
Number of pages9
JournalDevelopment
Volume137
Issue number7
DOIs
Publication statusPublished - 2010 Apr 1

Keywords

  • Chondrogenesis
  • Mouse
  • Runx
  • Sternum

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Runx1 and runx2 cooperate during sternal morphogenesis'. Together they form a unique fingerprint.

  • Cite this

    Kimura, A., Inose, H., Yano, F., Fujita, K., Ikeda, T., Sato, S., Iwasaki, M., Jinno, T., Ae, K., Fukumoto, S., Takeuchi, Y., Itoh, H., Imamura, T., Kawaguchi, H., Chung, U. I., Martin, J. F., Iseki, S., Shinomiya, K. I., & Takeda, S. (2010). Runx1 and runx2 cooperate during sternal morphogenesis. Development, 137(7), 1159-1167. https://doi.org/10.1242/dev.045005