Spatiotemporal Expression of Wnt/β-catenin Signaling during Morphogenesis and Odontogenesis of Deciduous Molar in Miniature Pig.

Spatiotemporal Expression of Wnt/β-catenin Signaling during Morphogenesis and Odontogenesis of Deciduous Molar in Miniature Pig.
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小型猪乳磨牙形态发生和牙发育过程中 Wnt/β-catenin 信号传导的时空表达。

DOI:
10.7150/ijbs.20905
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发表时间:
2017
影响因子:
9.2
通讯作者:
Wang S
Wang S
中科院分区:
生物学2区
文献类型:
--
作者:
Wu X;Li Y;Wang F;Hu L;Li Y;Wang J;Zhang C;Wang S

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经典的Wnt/β-catenin信号通路在牙齿发生和早期牙齿发育中起重要作用。然而,Wnt/β-catenin信号在大型哺乳动物牙尖模式和牙冠钙化中的作用在很大程度上是未知的。由于小型猪牙齿的解剖结构和替换方式与人类相似,我们在以前的研究中使用小型猪作为动物模型。应用基因芯片技术研究了小型猪第三乳磨牙早期牙胚发育过程中Wnt基因的动态表达,发现Wnt基因的表达与牙胚发育密切相关。在本研究中,Wnt/β-catenin信号转导基因DM 3在帽状、早期钟状和晚期钟状(分泌)阶段的动态表达模式被确定。我们发现Lef 1和Axin 2在釉质结和下面的间充质区域表达。同时,Dkk 1在牙乳头周围和下部表达,形成潜在的Wnt信号梯度。β-Catenin、Axin 2和Lef 1在内釉上皮未分化细胞中表达较强,而在成釉细胞中表达较弱。此外,我们发现Wnt信号读出基因Lef 1和抑制剂Dkk 1在前成牙本质细胞中共表达。总之,Wnt信号的时空分布和潜在梯度可能有助于牙尖图案和牙冠钙化。这些数据可能会产生洞察未来的研究精确控制冠形态发生和再生的大型哺乳动物。
The canonical Wnt/β-catenin signaling pathway has been shown to play essential roles in tooth initiation and early tooth development. However, the role of Wnt/β-catenin signaling in cusp patterning and crown calcification in large mammals are largely unknown. In our previous study, miniature pigs were used as the animal model due to the similarity of tooth anatomy and replacement pattern between miniature pig and human. Dynamic gene expression of third deciduous molar (DM3) in miniature pig at early stages was profiled using microarray method and expression of Wnt genes was significantly correlate with odontogenesis. In the present study, dynamic expression patterns of Wnt/β-catenin signaling genes of DM3 at cap, early bell and late bell (secretory) stage were identified. We found that Lef1 and Axin2 were expressed in the enamel knot and underlying mesenchyme regions. Meanwhile, Dkk1 was expressed in the peripheral and lower parts of dental papilla, thus forming the potential Wnt signaling gradient. We also found that β-Catenin, Axin2 and Lef1 were expressed strongly in undifferentiated cells of the inner enamel epithelium (IEE), but weakly in differentiated ameloblasts. Furthermore, we found that both Wnt signaling read-out gene Lef1 and the inhibitor Dkk1 were co-expressed in the pre-odontoblasts. In conclusion, the spatiotemporal distribution and potential gradient of Wnt signaling may contribute to cusp patterning and crown calcification. These data may yield insight into future study of precise control of crown morphogenesis and regeneration in large mammals.
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