Effects of Usag-1 and Bmp7 deficiencies on murine tooth morphogenesis.
Effects of Usag-1 and Bmp7 deficiencies on murine tooth morphogenesis.
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DOI：
10.1186/s12861-016-0117-x
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发表时间：
2016-05-13
影响因子：
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通讯作者：
Bessho K
中科院分区：
文献类型：
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作者：
Saito K;Takahashi K;Asahara M;Kiso H;Togo Y;Tsukamoto H;Huang B;Sugai M;Shimizu A;Motokawa M;Slavkin HC;Bessho K
Wnt5a和Mrfzb1基因参与牙齿大小的调节，其在形态发生过程中的表达水平与Bmp7相似，包括牙齿形成的帽形和早期钟形阶段。我们之前报道过 Usag-1 缺陷小鼠形成了多余的上颌切牙。因此，我们假设 BMP7 和 USAG-1 信号分子可能在牙齿形态发生中发挥重要作用。在这项研究中，我们建立了双转基因小鼠来检查 Bmp7 和 Usag-1 之间的体内相互关系。我们使用微型计算机断层扫描 (micro-CT) 测量了成年 Bmp7-和 Usag-1-LacZ 敲入小鼠及其杂交后的 F2 代小鼠的下颌切牙的体积和横截面积。成年 Bmp7+/- 小鼠的下颌切牙明显大于野生型 (WT) 小鼠。成年 Usag-1−/− 小鼠的下颌切牙是所有检查基因型中最大的。在F2代中，这些基因的作用是相加的；使用广义线性模型，Bmp7+/- 与牙齿尺寸的增加最为密切相关，并且 Usag-1−/−Bmp7+/- 小鼠的下颌多生切牙的总面积显着大于 Usag-1−/−Bmp7 +/+ 小鼠的总面积。在胚胎第 15 天 (E15)，BrdU 检测表明，Bmp7+/- 胚胎的宫颈环标记指数显着高于 WT 胚胎。此外，Usag-1−/− 胚胎的标记指数明显是牙乳头检查的所有基因型中最高的。 Bmp7杂合小鼠的牙齿尺寸显着增加，表明牙齿尺寸是由特定基因表达控制的。我们的发现可能对再生医学和牙科的应用有用。本文的在线版本 (doi:10.1186/s12861-016-0117-x) 包含补充材料，可供授权用户使用。
Wnt5a and Mrfzb1 genes are involved in the regulation of tooth size, and their expression levels are similar to that of Bmp7 during morphogenesis, including during the cap and early bell stages of tooth formation. We previously reported that Usag-1-deficient mice form supernumerary maxillary incisors. Thus, we hypothesized that BMP7 and USAG-1 signaling molecules may play important roles in tooth morphogenesis. In this study, we established double genetically modified mice to examine the in vivo inter-relationships between Bmp7 and Usag-1. We measured the volume and cross-sectional areas of the mandibular incisors using micro-computed tomography (micro-CT) in adult Bmp7- and Usag-1-LacZ knock-in mice and their F2 generation upon interbreeding. The mandibular incisors of adult Bmp7+/− mice were significantly larger than those of wild-type (WT) mice. The mandibular incisors of adult Usag-1−/− mice were the largest of all genotypes examined. In the F2 generation, the effects of these genes were additive; Bmp7+/− was most strongly associated with the increase in tooth size using generalized linear models, and the total area of mandibular supernumerary incisors of Usag-1−/−Bmp7+/− mice was significantly larger than that of Usag-1−/−Bmp7 +/+ mice. At embryonic day 15 (E15), BrdU assays demonstrated that the labeling index of Bmp7+/− embryos was significantly higher than that of WT embryos in the cervical loop. Additionally, the labeling index of Usag-1−/− embryos was significantly the highest of all genotypes examined in dental papilla. Bmp7 heterozygous mice exhibited significantly increased tooth sizes, suggesting that tooth size was controlled by specific gene expression. Our findings may be useful in applications of regenerative medicine and dentistry. The online version of this article (doi:10.1186/s12861-016-0117-x) contains supplementary material, which is available to authorized users.