The role of TGF-beta signaling in regulating chondrogenesis and osteogenesis during mandibular development |
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Authors: | Oka Kyoko Oka Shoji Sasaki Tomoyo Ito Yoshihiro Bringas Pablo Nonaka Kazuaki Chai Yang |
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Affiliation: | a Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA b Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan |
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Abstract: | 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. |
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Keywords: | Cranial neural crest (CNC) Cell proliferation Differentiation Mandible and Meckel's cartilage development CTGF Msx1 TGF-β |
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