The inductive role of Wnt-β-Catenin signaling in the formation of oral apparatus.
The inductive role of Wnt-β-Catenin signaling in the formation of oral apparatus.
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DOI：
10.1016/j.ydbio.2011.05.002
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发表时间：
2011-08-01
影响因子：
2.7
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Lin C;Fisher AV;Yin Y;Maruyama T;Veith GM;Dhandha M;Huang GJ;Hsu W;Ma L
包括牙齿、舌头和上颚在内的口腔结构的正常模式和生长依赖于上皮-间质相互作用，包括信号转导的协调调节。了解支持口腔-面部发育的分子机制将为腭裂等常见先天性缺陷的病因学提供新的见解。在这项研究中，我们报道了在口腔上皮中切除Wnt信号会阻断腭纹的形成，腭纹是一组特化的外胚层附着物，在发育过程中充当Shh信号中心，并可能在成人中充当感觉细胞和神经嵴相关干细胞的龛。缺乏皱褶也与硬腭前后伸展迟缓和中线融合早熟有关。这些数据暗示了典型Wnt信号在规则发展中的重要作用。基于这种复杂的表型，我们提出rugae及其形态因子Shh的顺序添加与硬腭的伸长内在耦合，并且对调节腭架的生长方向至关重要。此外，我们观察到一种独特的腭裂表型在第二腭的前端，这可能是由于这些突变体的初级腭严重不发达造成的。最后但并非最不重要的是，我们还发现Wnt和Shh信号对舌头发育都是必不可少的。我们提供的遗传证据表明，任何信号通路的破坏导致严重的微语缺失。总之，我们证明了Wnt-β-Catenin信号在口腔器官发育中的动态作用。
Proper patterning and growth of oral structures including teeth, tongue, and palate rely on epithelial-mesenchymal interactions involving coordinated regulation of signal transduction. Understanding molecular mechanisms underpinning oral-facial development will provide novel insights into the etiology of common congenital defects such as cleft palate. In this study, we report that ablating Wnt signaling in the oral epithelium blocks the formation of palatal rugae, which are a set of specialized ectodermal appendages serving as Shh signaling centers during development and niches for sensory cells and possibly neural crest related stem cells in adults. Lack of rugae is also associated with retarded anteroposterior extension of the hard palate and precocious mid-line fusion. These data implicate an obligatory role for canonical Wnt signaling in rugae development. Based on this complex phenotype, we propose that the sequential addition of rugae and its morphogen Shh, is intrinsically coupled to the elongation of the hard palate, and is critical for modulating the growth orientation of palatal shelves. In addition, we observe a unique cleft palate phenotype at the anterior end of the secondary palate, which is likely caused by the severely underdeveloped primary palate in these mutants. Last but not least, we also discover that both Wnt and Shh signalings are essential for tongue development. We provide genetic evidence that disruption of either signaling pathway results in severe microglossia. Altogether, we demonstrate a dynamic role for Wnt-β-Catenin signaling in the development of the oral apparatus.
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