Developmental expression of Smad1-7 suggests critical function of TGF-beta/BMP signaling in regulating epithelial-mesenchymal interaction during tooth morphogenesis.
Developmental expression of Smad1-7 suggests critical function of TGF-beta/BMP signaling in regulating epithelial-mesenchymal interaction during tooth morphogenesis.
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DOI：
10.1387/14
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发表时间：
2003-02
期刊：
影响因子：
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通讯作者：
Xun Xu;Lesley Y. Jeong;Jun Han;Yoshihiro Ito;P. Bringas;Y. Chai
中科院分区：
文献类型：
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作者：
Xun Xu;Lesley Y. Jeong;Jun Han;Yoshihiro Ito;P. Bringas;Y. Chai
转化生长因子-β家族的成员（例如TGF-β、BMP和激活素）是牙齿形态发生的关键调节剂。基本的TGF-β信号传导引擎由激活Smads的受体复合物和控制下游靶基因转录的含Smad复合物组成。关于内源性Smads在牙齿形态发生过程中的表达知之甚少。使用cRNA探针或抗体，特异性地识别每个Smad分子的表达，我们提供了一个全面的内源性Smad在牙齿形态发生的表达分析。BMP信号通过Smad 1和Smad 5传递，Smad 1和Smad 5首先在牙板内表达，然后在芽期扩展到致密的牙间充质中。随着牙齿发育进入帽状和钟状阶段，BMP信号Smads强烈定位于内釉上皮（IEE）和颅神经嵴衍生的牙间充质（DM），表明它们在牙齿形态发生过程中调节上皮-间充质相互作用的关键作用。Smad 2和3负责传递TGF-β/激活素信号，并在牙齿形态发生过程中显示出独特的表达模式。它们位于IEE和DM的细胞核内，表明TGF-β激活的Smads对调节牙齿发育至关重要。Smad 4是常见的Smad，在牙齿形态发生的所有阶段都在牙上皮和间充质中表达。抑制性Smads（Smad 6和7）的表达与受体调节的Smads在很大程度上重叠，表明BMP/TGF-β信号传导的负反馈在牙齿形态发生的所有阶段都是至关重要的。我们的研究结果表明，受体调节和抑制Smads是牙齿形态发生的重要调节剂。Smad的选择性激活，如核转位所示，可能表明在牙齿发育过程中TGF-β超家族的不同成员的选择性激活。
Members of the transforming growth factor-beta family (e.g. TGF-beta, BMP and activin) are critical regulators of tooth morphogenesis. The basic TGF-beta signaling engine consists of a receptor complex that activates Smads and a Smad-containing complex that controls transcription of the downstream target genes. Little is known about the expression of endogenous Smads during tooth morphogenesis. Using a cRNA probe or antibody which specifically recognizes the expression of each Smad molecule, we provide a comprehensive endogenous Smad expression analysis during tooth morphogenesis. BMP signaling is transmitted through Smad1 and 5 which are first expressed within the dental lamina and later expand into condensed dental mesenchyme at the bud stage. As tooth development advances into the cap and bell stage, BMP signaling Smads are strongly localized within the inner enamel epithelium (IEE) and cranial neural crest derived dental mesenchyme (DM), indicating their critical role in regulating epithelial-mesenchyme interaction during tooth morphogenesis. Smad2 and 3 are responsible for transmitting TGF-beta/activin signaling and show unique expression patterns during tooth morphogenesis. They are localized within the nuclei of both IEE and DM, suggesting that TGF-beta-activated Smads are critical for regulating tooth development. Smad4, the common Smad, is expressed in both dental epithelium and mesenchyme throughout all stages of tooth morphogenesis. The expression of inhibitory Smads (Smad6 and 7) largely overlaps with receptor regulated Smads, indicating that negative feedback on BMP/TGF-beta signaling is critical throughout all stages of tooth morphogenesis. Our results suggest that both receptor-regulated and inhibitory Smads are important regulators of tooth morphogenesis. The selective activation of Smad, as indicated by nucleartranslocation, may suggest selective activation of different members of the TGF-beta superfamily during tooth development.