Noggin Is Required for Early Development of Murine Upper Incisors
Noggin Is Required for Early Development of Murine Upper Incisors
复制标题
小鼠上门牙的早期发育需要 Noggin
DOI：
10.1177/0022034511435939
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发表时间：
2012-04-01
影响因子：
7.6
通讯作者：
Chen, Y. P.
中科院分区：
文献类型：
--
作者：
Hu, X.;Wang, Y.;Chen, Y. P.
BMP信号在包括牙齿在内的许多器官的发育过程中起着至关重要的作用。同样重要的是BMP信号的动态平衡，正如缺乏细胞外BMP拮抗剂Noggin的小鼠的多个器官缺陷所证明的那样。在这里，我们发现Noggin最初在上颌切牙附属的上颌间充质中表达，然后从萌发期开始在发育中的牙齿，包括门牙和磨牙中表达。Noggin突变体发育出正常的磨牙和下颌门牙，但形成单一的位于中部的上门牙，在蕾期晚期停止。组织学和分子标记分析表明，两个不同的上切牙胎盘在E11.5开始独立启动，但在E12.5开始融合，并伴随着发育中的牙胚细胞增殖率的提高。我们进一步发现，另外两种BMP拮抗剂Chordin和Gremlin在发育中的下切牙和磨牙中与Noggin共表达。这些观察表明了BMP信号动态平衡的重要性，并提示在牙齿发育过程中BMP拮抗剂之间存在功能冗余。
BMP signaling plays crucial roles in the development of many organs, including the tooth. Equally important is BMP signaling homeostasis, as demonstrated by multiple organ defects in mice lacking the extracellular BMP antagonist Noggin. Here, we show that Noggin is initially expressed in the maxillary mesenchyme adjunct to the upper incisor at the initiation stage, and then in the developing teeth, including incisors and molars, from the bud stage. Noggin mutants develop normal molars and mandibular incisors, but form a single, medially located upper incisor that is arrested at the late bud stage. Histological and molecular marker analyses demonstrated that two distinct upper incisor placodes initiate independently at E11.5, but begin to fuse at E12.5, coupling with elevated cell proliferation rates in the developing tooth germs. We further found that Chordin and Gremlin, two other BMP antagonists, are co-expressed with Noggin in the developing lower incisor and molar teeth. These observations indicate the importance of BMP signaling homeostasis, and suggest a functional redundancy between BMP antagonists during tooth development.