The role of TGF-β signaling in regulating chondrogenesis and osteogenesis during mandibular development
The role of TGF-β signaling in regulating chondrogenesis and osteogenesis during mandibular development
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DOI：
10.1016/j.ydbio.2006.11.025
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发表时间：
2007-03-01
影响因子：
2.7
通讯作者：
Chai, Yang
中科院分区：
文献类型：
--
作者：
Oka, Kyoko;Oka, Shoji;Chai, Yang
在颅面发育过程中，Meckel软骨和下颌骨来源于第一鳃弓，它们的发育取决于颅神经嵴（CNC）细胞的贡献。我们以前证明，在小鼠的神经嵴（Tg 1br 2（fl/fl）; Wnt 1-Cre）的条件失活Tgfbr 2的结果在下颌骨发育的严重缺陷，虽然特定的细胞和分子机制，TGF-β信号调节CNC细胞的命运在下颌骨发育过程中仍然未知。我们在这里表明，Tgfbr 2的损失并不影响迁移的CNC细胞在下颌骨发育。Meckel软骨和下颌骨原基中的细胞增殖以及冠状突、髁突和角突的形成特别需要TGF-β信号传导。TGF-β介导的结缔组织生长因子（CTGF）信号传导对于CNC细胞增殖至关重要。外源性CTGF挽救了Tglbr 2（fl/fl）; Wnt 1-Cre突变体的Meckel软骨中的细胞增殖缺陷，证明了这种信号级联在下颌骨发育期间的软骨形成中的生物学意义。此外，TGF-β信号传导控制Msx 1表达以调节下颌骨成骨，因为Msx 1表达在Tglbr 2（fl/fl）; Wnt 1-Cre突变体中显著降低。总的来说，我们的数据表明，在下颌骨发育过程中，有不同的信号级联反应TGF-β控制软骨和骨生成。(c)2006年爱思唯尔公司All rights reserved.
During cramofacial 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 (Tg1br2(fl/fl);Wnt1-Cre) results in severe defects in mandibular development, although the specific cellular and molecular mechanisms by which TGF-beta 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-beta 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-beta-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 Tglbr2(fl/fl); Wnt1-Cre mutants, demonstrating the biological significance of this signaling cascade in chondrogenesis during mandibular development. Furthermore, TGF-beta signaling controls Msx1 expression to regulate mandibular osteogenesis as Msx1 expression is significantly reduced in Tglbr2(fl/fl);Wnt1-Cre mutants. Collectively, our data suggest that there are differential signal cascades in response to TGF-beta to control chondrogenesis and osteogenesis during mandibular development. (c) 2006 Elsevier Inc. All rights reserved.