Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth

Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth
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DOI:
10.1006/dbio.1998.8992
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发表时间:
1998-10-15
影响因子:
2.7
通讯作者:
McMahon, AP
McMahon, AP
中科院分区:
生物学3区
文献类型:
--
作者:
Dassule, HR;McMahon, AP

文献摘要

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上皮-间充质相互作用支配着牙齿等表皮器官的发育。在牙齿发育的早期阶段,局部外胚层增厚,表达几种信号分子。据信,这反过来又向潜在的间质发出信号,触发间质凝结和牙齿发育。例如,上皮表达的Bmp4诱导Msx1和Lef1以及自身在下层间质中表达。在本文中,我们研究了四个上皮信号分子,Bmp2, Shh, Wnt10a和Wnt10b,在控制牙齿发育的早期诱导级联反应中的作用。我们发现所有四个基因在E11.0和E12.0之间的上皮中特异性表达,此时牙齿形态发生首次明显。尽管Shh、Bmp2和Wnt10b具有相似的(如果不是完全相同的话)表达模式,但每个信号在颚间质上都有不同的分子作用。而Shh和Wnt10b可以诱导一般的Hedgehog和Wnt靶标,Ptc和Gli可以诱导Shh和I;在Wnt10b中,只有Bmp2能够诱导Msx1的牙齿特异性表达。因此,这三种途径都有不同的靶点。有趣的是,Bmp和Wnt信号都激活了Lef1,使其成为整合两种不同信号通路的候选者。(C) 1998学术出版社。
Epithelial-mesenchymal interactions govern the development of epidermal organs such as teeth. During the early stages of tooth development, a local ectodermal thickening which expresses several signaling molecules appears. It is believed that these in turn signal to the underlying mesenchyme triggering mesenchymal condensation and tooth development. For example, epithelially expressed Bmp4 induces Msx1 and Lef1 as well as itself in the underlying mesenchyme. In this paper we have investigated the role of four epithelial signaling molecules, Bmp2, Shh, Wnt10a, and Wnt10b, in the early inductive cascades that govern tooth development. We show that all four genes are specifically expressed in the epithelium between E11.0 and E12.0 when tooth morphogenesis is first apparent. Although Shh, Bmp2, and Wnt10b have similar, if not identical, expression patterns, each signal has a distinct molecular action on the jaw mesenchyme. Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets, Ptc and Gli for Shh and I;efl for Wnt10b, only Bmp2 is able to induce tooth-specific expression of Msx1. Thus, there are distinct targets for all three pathways. Interestingly, both Bmp and Wnt signaling activate Lef1, making it a candidate for integrating the two distinct signaling pathways. (C) 1998 Academic Press.