Coordination of trigeminal axon navigation and patterning with tooth organ formation:: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfβ1 regulate semaphorin 3a expression in the dental mesenchyme
Coordination of trigeminal axon navigation and patterning with tooth organ formation:: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfβ1 regulate semaphorin 3a expression in the dental mesenchyme
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DOI：
10.1242/dev.01541
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发表时间：
2005-01-01
期刊：
影响因子：
4.6
通讯作者：
Luukko, K
中科院分区：
文献类型：
--
作者：
Kettunen, P;Loes, S;Luukko, K
在发育过程中，三叉神经纤维以高度时空控制的方式导航并建立其轴突投射到发育中的牙齿。通过分析 Sema3a 及其受体 Npn1 敲除小鼠胚胎，我们发现 Sema3a 调节牙齿三叉神经轴突的导航和模式，以及第一下颌磨牙神经支配的时间，并且 Sema3a 的作用似乎是由轴突中存在的 Npn1 介导的。通过进行组织重组实验并分析信号分子的影响，我们发现指导牙齿形成的早期口腔和牙齿上皮以及上皮 Wnt4 在第一根牙神经纤维到达之前诱导假定的牙齿间充质中的 Sema3a 表达。随后，在芽期，上皮 Wnt4 和 Tgfbeta1 调节牙齿间充质中的 Sema3a 表达。此外，Wnt4 刺激 Msx1 转录因子的间充质表达，这对于牙齿形成和牙齿间充质细胞的 Tgfbeta1 增殖至关重要。因此，上皮-间质相互作用控制 Sema3a 表达，并可能协调轴突导航和模式与牙齿形成。此外，我们的结果表明牙源上皮拥有控制牙神经供应形成的指导信息。
During development, trigeminal nerve fibers navigate and establish their axonal projections to the developing tooth in a highly spatiotemporally controlled manner. By analyzing Sema3a and its receptor Npn1 knockout mouse embryos, we found that Sema3a regulates dental trigeminal axon navigation and patterning, as well as the timing of the first mandibular molar innervation, and that the effects of Sema3a appear to be mediated by Npn1 present in the axons. By performing tissue recombinant experiments and analyzing the effects of signaling molecules, we found that early oral and dental epithelia, which instruct tooth formation, and epithelial Wnt4 induce Sema3a expression in the presumptive dental mesenchyme before the arrival of the first dental nerve fibers. Later, at the bud stage, epithelial Wnt4 and Tgfbeta1 regulate Sema3a expression in the dental mesenchyme. In addition, Wnt4 stimulates mesenchymal expression of Msx1 transcription factor, which is essential for tooth formation, and Tgfbeta1 proliferation of the dental mesenchymal cells. Thus, epithelial-mesenchymal interactions control Sema3a expression and may coordinate axon navigation and patterning with tooth formation. Moreover, our results suggest that the odontogenic epithelium possesses the instructive information to control the formation of tooth nerve supply.