Cell autonomous requirement for TGF-β signaling during odontoblast differentiation and dentin matrix formation

Cell autonomous requirement for TGF-β signaling during odontoblast differentiation and dentin matrix formation
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DOI:
10.1016/j.mod.2007.02.003
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发表时间:
2007-07-01
影响因子:
2.6
通讯作者:
Chai, Yang
Chai, Yang
中科院分区:
生物学4区
文献类型:
--
作者:
Oka, Shoji;Oka, Kyoko;Chai, Yang

文献摘要

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TGF-β亚型在小鼠颅面发育早期颅神经嵴细胞来源的组织中表达。TGF-β信号传导对于介导上皮-间充质相互作用至关重要,包括对牙齿形态发生至关重要的那些。然而,目前还不清楚TGF-β信号通路如何有助于牙齿形态发生过程中的成牙本质细胞和牙本质形成的终末分化。为此,我们产生了Tgfbr 2基因在颅神经嵴衍生细胞中条件性失活的小鼠。在E18.5时,Tgfbr 2(fl/fl); Wnt1-Cre突变小鼠的成牙本质细胞分化显著延迟。在肾包膜移植后,Tgfbr 2突变牙胚表达的Co11a1和Dspp水平降低,并表现出缺陷,包括牙本质厚度减少和牙本质小管缺失。此外,在Tgfbr 2突变体样品中,中间丝巢蛋白的表达降低。值得注意的是,外源性TGF-β 2诱导巢蛋白和Dspp表达的牙髓细胞在发育中的牙齿器官。我们的数据表明,TGF-β信号控制成牙本质细胞的成熟和牙本质形成在牙齿形态发生。(c)2007 Flsevier爱尔兰有限公司保留所有权利。
TGF-beta subtypes are expressed in tissues derived from cranial neural crest cells during early mouse craniofacial development. TGF-beta signaling is critical for mediating epithelial-mesenchymal interactions, including those vital for tooth morphogenesis. However, it remains unclear how TGF-beta signaling contributes to the terminal differentiation of odontoblast and dentin formation during tooth morphogenesis. Towards this end, we generated mice with conditional inactivation of the Tgfbr2 gene in cranial neural crest derived cells. Odontoblast differentiation was substantially delayed in the Tgfbr2(fl/fl); Wnt1-Cre mutant mice at E18.5. Following kidney capsule transplantation, Tgfbr2 mutant tooth germs expressed a reduced level of Co11a1 and Dspp and exhibited defects including decreased dentin thickness and absent dentinal tubules. In addition, the expression of the intermediate filament nestin was decreased in the Tgfbr2 mutant samples. Significantly, exogenous TGF-beta 2 induced nestin and Dspp expression in dental pulp cells in the developing tooth organ. Our data suggest that TGF-beta signaling controls odontoblast maturation and dentin formation during tooth morphogenesis. (c) 2007 Flsevier Ireland Ltd. All rights reserved.