Msx1 controls inductive signaling in mammalian tooth morphogenesis.
Msx1 controls inductive signaling in mammalian tooth morphogenesis.
复制标题
DOI：
10.1242/dev.122.10.3035
复制
发表时间：
1996-10
期刊：
影响因子：
4.6
通讯作者：
YiPing Chen;Marianna Bei;I. Woo;I. Satokata;Richard L. Maas
中科院分区：
文献类型：
--
作者：
YiPing Chen;Marianna Bei;I. Woo;I. Satokata;Richard L. Maas
Msx同源框家族成员被认为在脊椎动物器官发生过程中的诱导组织相互作用中发挥重要作用，但其确切的发育功能尚不清楚。缺乏Msx 1的小鼠表现出颅面发育缺陷和牙齿形态发生失败，在E13.5芽期臼齿发育停滞。由于其潜在的实验操作，鼠磨牙牙胚提供了一个强大的系统，用于研究Msx基因在器官发生过程中诱导信号传导的作用。为了进一步分析Msx 1在牙齿形态发生过程中调节上皮-间充质相互作用的作用，我们研究了几个潜在的Msx 1下游基因在Msx 1突变牙胚中的表达，并进行了旨在将这些基因排列成通路的功能实验。我们的研究结果表明，骨形态发生蛋白4（BMP 4），HMG盒基因Lef 1和硫酸乙酰肝素蛋白聚糖syndecan-1的表达在Msx 1突变体牙间充质中特异性降低，而细胞外基质蛋白生腱蛋白的表达不受影响。BMP 4浸泡的微珠可以诱导Bmp 4和Lef 1在缺失的野生型牙间充质中表达，但只能诱导Lef 1在Msx 1突变型牙间充质中表达。因此，我们得出结论，上皮BMP 4诱导其自身的表达在牙齿间充质中的方式，需要Msx 1。反过来，我们表明，除了BMP 4的Msx 1缺陷的牙胚绕过Msx 1的要求和救援上皮发育从芽阶段到E14.5帽阶段。最后，我们表明，FGF诱导syndecan-1在牙齿间充质中的表达的方式，也需要Msx-1。这些结果将Msx 1整合到早期牙齿形态发生的调控层次中，并表明Msx 1不仅在牙间充质中响应上皮信号表达，而且还反过来调控间充质中诱导信号的相互表达，然后作用于牙上皮。我们建议，Msx基因的功能重复在脊椎动物器官发生，使诱导信号发生之间的组织层。
Members of the Msx homeobox family are thought to play important roles in inductive tissue interactions during vertebrate organogenesis, but their precise developmental function has been unclear. Mice deficient for Msx1 exhibit defects in craniofacial development and a failure of tooth morphogenesis, with an arrest in molar tooth development at the E13.5 bud stage. Because of its potential for experimental manipulation, the murine molar tooth germ provides a powerful system for studying the role of Msx genes in inductive signaling during organogenesis. To further analyze the role of Msx1 in regulating epithelial-mesenchymal interactions during tooth morphogenesis, we have examined the expression of several potential Msx1 downstream genes in Msx1 mutant tooth germs and we have performed functional experiments designed to order these genes into a pathway. Our results show that expression of Bone Morphogenetic Protein 4 (BMP4), the HMG box gene Lef1 and the heparan sulfate proteoglycan syndecan-1 is specifically reduced in Msx1 mutant dental mesenchyme, while expression of the extracellular matrix protein tenascin is unaffected. BMP4 soaked beads can induce Bmp4 and Lef1 expression in explanted wild-type dental mesenchymes, but only Lef1 expression in Msx1 mutant dental mesenchyme. We thus conclude that epithelial BMP4 induces its own expression in dental mesenchyme in a manner that requires Msx1. In turn, we show that addition of BMP4 to Msx1 deficient tooth germs bypasses the requirement for Msx1 and rescues epithelial development from the bud stage to the E14.5 cap stage. Lastly, we show that FGFs induce syndecan-1 expression in dental mesenchyme in a manner that also requires Msx-1. These results integrate Msx1 into a regulatory hierarchy in early tooth morphogenesis and demonstrate that Msx1 is not only expressed in dental mesenchyme in response to epithelial signals, but also in turn regulates the reciprocal expression of inductive signals in the mesenchyme which then act back upon the dental epithelium. We propose that Msx genes function repetitively during vertebrate organogenesis to permit inductive signaling to occur back and forth between tissue layers.