Activin is an essential early mesenchymal signal in tooth development that is required for patterning of the murine dentition
Activin is an essential early mesenchymal signal in tooth development that is required for patterning of the murine dentition
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DOI：
10.1101/gad.12.16.2636
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发表时间：
1998-08-15
影响因子：
10.5
通讯作者：
Sharpe, PT
中科院分区：
文献类型：
--
作者：
Ferguson, CA;Tucker, AS;Sharpe, PT
哺乳动物牙齿的发育作为器官发生过程中上皮/间充质相互作用的模型系统已被深入研究，并且在确定参与这种信号传导的关键分子方面取得了进展。我们发现激活素PA在假定的牙胚间充质中表达，因此是牙齿发育中信号分子的候选者。对激活素β A突变胚胎中牙齿发育的分析表明，门齿和下颌磨牙不能发育到芽期之后。因此，激活素PA是牙齿发育的重要组成部分。然而，在突变体中，上颌磨牙的发育不受影响。使用组织重组实验，我们表明，在芽形成之前，间充质中需要激活素，并且尽管发生了从间充质到上皮的激活素信号传导，但突变的上皮保留了其支持牙齿发育的能力。将浸泡在激活素A中的珠粒植入发育中的下颌骨中，能够完全挽救E11.5的牙齿发育，但不能挽救E12.5或E13.5的牙齿发育，证实激活素是牙芽形成前所需的早期、必需的间充质信号。在没有激活素的情况下上颌磨牙的正常发育显示了该途径在牙列发育中的位置特异性作用。激活素B或其他TGP β家族成员与激活素受体结合的功能冗余不能解释突变体中上颌磨牙的发育，因为激活素信号通路在这些牙胚中似乎不活跃。激活素信号在切牙和下颌磨牙牙胚间充质中的早期需求必须通过其他独立的信号通路在上颌磨牙间充质中进行。
Development of the mammalian tooth has been intensively studied as a model system far epithelial/mesenchymal interactions during organogenesis, and progress has been made in identifying key molecules involved in this signaling. We show that activin PA is expressed in presumptive tooth-germ mesenchyme and is thus a candidate for a signaling molecule in tooth development. Analysis of tooth development in activin beta A mutant embryos shows that incisor and mandibular molar teeth fail to develop beyond the bud stage. Activin PA is thus an essential component of tooth development. Development of maxillary molars, however, is unaffected in the mutants. Using tissue recombination experiments we show that activin is required in the mesenchyme prior to bud formation and that although activin signaling from mesenchyme to epithelium takes place, mutant epithelium retains its ability to support tooth development, Implantation of beads soaked in activin A, into developing mandibles, is able to completely rescue tooth development from E11.5, but not E12.5 or E13.5, confirming that activin is an early, essential mesenchyme signal required before tooth bud formation. Normal development of maxillary molars in the absence of activin shows a position specific role for this pathway in development of dentition. Functional redundancy With activin B or other TGP beta family members that bind to activin receptors cannot explain development of maxillary molars in the mutants since the activin-signaling pathway appears not to be active in these tooth germs. The early requirement for activin signaling in the mesenchyme in incisor and mandibular molar tooth germs must be carried-out in maxillary molar mesenchyme by other independent signaling pathways.