The role of TGF-β signaling in regulating chondrogenesis and osteogenesis during mandibular development

Kyoko Oka, Shoji Oka, Tomoyo Sasaki, Yoshihiro Ito, Pablo Bringas, Kazuaki Nonaka, Yang Chai

研究成果: Contribution to journalArticle査読

105 被引用数 (Scopus)


During craniofacial development, Meckel's cartilage and the mandible bone derive from the first branchial arch, and their development depends upon the contribution of cranial neural crest (CNC) cells. We previously demonstrated that conditional inactivation of Tgfbr2 in the neural crest of mice (Tgfbr2fl/fl;Wnt1-Cre) results in severe defects in mandibular development, although the specific cellular and molecular mechanisms by which TGF-β signaling regulates the fate of CNC cells during mandibular development remain unknown. We show here that loss of Tgfbr2 does not affect the migration of CNC cells during mandibular development. TGF-β signaling is specifically required for cell proliferation in Meckel's cartilage and the mandibular anlagen and for the formation of the coronoid, condyle and angular processes. TGF-β-mediated connective tissue growth factor (CTGF) signaling is critical for CNC cell proliferation. Exogenous CTGF rescues the cell proliferation defect in Meckel's cartilage of Tgfbr2fl/fl;Wnt1-Cre mutants, demonstrating the biological significance of this signaling cascade in chondrogenesis during mandibular development. Furthermore, TGF-β signaling controls Msx1 expression to regulate mandibular osteogenesis as Msx1 expression is significantly reduced in Tgfbr2fl/fl;Wnt1-Cre mutants. Collectively, our data suggest that there are differential signal cascades in response to TGF-β to control chondrogenesis and osteogenesis during mandibular development.

ジャーナルDevelopmental Biology
出版ステータス出版済み - 3 1 2007

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学
  • 細胞生物学


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