Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice.
Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice.
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发表时间：
1999-07
期刊：
影响因子：
4.6
通讯作者：
Rena N. D'Souza;T. Åberg;Joel S. Gaikwad;A. Cavender;Michael J. Owen;Gerard Karsenty;I. Thesleff
中科院分区：
文献类型：
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作者：
Rena N. D'Souza;T. Åberg;Joel S. Gaikwad;A. Cavender;Michael J. Owen;Gerard Karsenty;I. Thesleff
成骨细胞和成牙本质细胞分别负责形成骨和牙本质基质，它们具有一些共同的分子特征。最近，Cbfa1被证明是成骨细胞分化的关键转录调节因子。该基因的突变会导致锁骨颅骨发育不良（CCD），这是人类和小鼠的一种常染色体显性遗传疾病，其特征是骨形成缺陷。 CCD 还会导致牙齿缺陷，包括多生牙和恒牙列萌出延迟。 CCD 中的牙齿异常表明该分子在牙列形成中发挥着重要作用。在这里，我们描述了旨在了解 Cbfa1 在牙齿形成中的功能的研究结果。 RT-PCR和原位杂交分析表明，在活跃的上皮形态发生过程中，Cbfa1在从芽期到早期钟形阶段的牙齿间充质中具有独特的表达模式。与成骨细胞分化中观察到的不同，Cbfa1 在完全分化的成牙本质细胞中下调，并且在牙釉质形成的成熟阶段令人惊讶地在外胚层衍生的成釉细胞中表达。 Cbfa1-/- 小鼠畸形和严重发育不全的牙齿器官进一步说明了 Cbfa1 在牙齿形态发生中的作用。这些牙齿器官缺乏明显的成牙本质细胞和成釉细胞分化以及正常的牙本质和牙釉质基质。上皮-间质重组表明，牙上皮在芽期和冠期调节间充质 Cbfa1 表达，并且这些效应由 FGF 模拟，但不是由 BMP 模拟，如我们的珠植入测定所示。我们认为 Cbfa1 调节间充质分子的表达，这些分子与牙上皮相互作用，控制其生长和分化。综上所述，我们的数据表明 Cbfa1 在牙齿发育中的非冗余作用可能与骨形成中的作用不同。在牙发生过程中，Cbfa1 不参与调节牙齿萌生和早期形态发生的早期信号网络，但调节关键的上皮-间质相互作用，控制上皮牙釉质器官的形态发生和组织分化。
Osteoblasts and odontoblasts, cells that are responsible for the formation of bone and dentin matrices respectively, share several molecular characteristics. Recently, Cbfa1 was shown to be a critical transcriptional regulator of osteoblast differentiation. Mutations in this gene cause cleidocranial dysplasia (CCD), an autosomal dominant disorder in humans and mice characterized by defective bone formation. CCD also results in dental defects that include supernumerary teeth and delayed eruption of permanent dentition. The dental abnormalities in CCD suggest an important role for this molecule in the formation of dentition. Here we describe results of studies aimed at understanding the functions of Cbfa1 in tooth formation. RT-PCR and in situ hybridization analyses show that Cbfa1 has a unique expression pattern in dental mesenchyme from the bud to early bell stages during active epithelial morphogenesis. Unlike that observed in osteoblast differentiation, Cbfa1 is downregulated in fully differentiated odontoblasts and is surprisingly expressed in ectodermally derived ameloblasts during the maturation phase of enamel formation. The role of Cbfa1 in tooth morphogenesis is further illustrated by the misshapen and severely hypoplastic tooth organs in Cbfa1-/- mice. These tooth organs lacked overt odontoblast and ameloblast differentiation and normal dentin and enamel matrices. Epithelial-mesenchymal recombinants demonstrate that dental epithelium regulates mesenchymal Cbfa1 expression during the bud and cap stages and that these effects are mimicked by the FGFs but not by the BMPs as shown by our bead implantation assays. We propose that Cbfa1 regulates the expression of molecules in mesenchyme that act reciprocally on dental epithelium to control its growth and differentiation. Taken together, our data indicate a non-redundant role for Cbfa1 in tooth development that may be distinct from that in bone formation. In odontogenesis, Cbfa1 is not involved in the early signaling networks regulating tooth initiation and early morphogenesis but regulates key epithelial-mesenchymal interactions that control advancing morphogenesis and histodifferentiation of the epithelial enamel organ.