Bmp signaling in molar cusp formation
Bmp signaling in molar cusp formation
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DOI：
10.1016/j.gep.2019.04.002
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发表时间：
2019-06-01
影响因子：
1.2
通讯作者：
Ohazama, Atsushi
中科院分区：
文献类型：
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作者：
Meguro, Fumiya;Porntaveetus, Thantrira;Ohazama, Atsushi
牙尖是一个至关重要的结构，因为臼齿的形状是由牙尖的数量、形状和大小决定的。骨形态发生蛋白（Bone morphogenetic protein, Bmp）信号在牙齿发育过程中起着至关重要的作用。然而，目前尚不清楚Bmp信号是否也参与了尖的形成。为了解决这个问题，我们在两种不同的转基因小鼠系中检测了cusp: Bmp4 （K14-Bmp4）过表达的小鼠，以及角化蛋白14 （K14）启动子下Bmp抑制剂Noggin （K14-Noggin）的小鼠。K14-Noggin小鼠显示出额外的尖头，而K14-Bmp4小鼠观察到的尖头数量减少。为了进一步了解Bmps在尖牙形成过程中的表达方式，我们对E14.5至P3期小鼠上颌和下颌磨牙的三种主要Bmps （Bmp2、Bmp4和Bmp7）进行了全贴装原位杂交分析。E14.5时上颌磨牙Bmp2和Bmp4均呈线性表达。在E16.5时，Bmp2和Bmp4在上颌磨牙和下颌磨牙的表达模式有显著差异。P3时，所有Bmps在上颌磨牙尖区均有表达；然而，模式有所不同。因此，所有的Bmps在尖端形成过程中都表现出动态的时空表达。因此可以推断Bmp信号参与调节尖的形成。
Tooth cusp is a crucial structure, since the shape of the molar tooth is determined by number, shape, and size of the cusp. Bone morphogenetic protein (Bmp) signaling is known to play a critical role in tooth development, including in initiation. However, it remains unclear whether Bmp signaling is also involved in cusp formation. To address this question, we examined cusp in two different transgenic mouse lines: mice with overexpression of Bmp4 (K14-Bmp4), and those with Bmp inhibitor, Noggin, (K14-Noggin) under keratin14 (K14) promoter. K14-Noggin mice demonstrated extra cusps, whereas reduced number of cusps was observed in K14-Bmp4 mice. To further understand how Bmps are expressed during cusp formation, we performed whole-mount in situ hybridisation analysis of three major Bmps (Bmp2, Bmp4, and Bmp7) in murine maxillary and mandibular molars from E14.5 to P3. The linear expressions of Bmp2 and Bmp4 were observed in both maxillary and mandibular molars at E14.5. The expression patterns of Bmp2 and Bmp4 became significantly different between the maxillary and mandibular molars at E16.5. At P3, all Bmps were expressed in all the cusp regions of the maxillary molar; however, the patterns differed. All Bmps thus exhibited dynamic temporo-spatial expression during the cusp formation. It could therefore be inferred that Bmp signaling is involved in regulating cusp formation.