Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) expression and possible function in mouse tooth germ development
Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) expression and possible function in mouse tooth germ development
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DOI：
10.1007/s10735-016-9680-5
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发表时间：
2016-08-01
影响因子：
3.2
通讯作者：
Kiyoshima, Tamotsu
中科院分区：
文献类型：
--
作者：
Hasegawa, Kana;Wada, Hiroko;Kiyoshima, Tamotsu
面肩肱型肌营养不良症（FSHD）区域基因1（FRG 1）的异常表达参与了FSHD的发病。FRG 1对正常的肌肉和血管发育也很重要。我们前期的研究表明，FRG 1基因在胚胎10.5天（E10.5）的下颌骨中的表达高于E12.0。在这项研究中，我们调查的时空表达模式的FRG 1 mRNA和蛋白在小鼠下第一磨牙的发展过程中，也评估了亚细胞定位的FRG 1蛋白在小鼠牙上皮细胞（mDE6）。FRG 1在牙胚上皮细胞和间充质细胞中的表达在牙胚发育的起始期和芽生期都有表达。在帽状期和钟状早期的内釉上皮中检测到。在钟状和牙根形成后期，这些信号分别在釉质和牙本质基质形成期间的成釉细胞和成牙本质细胞中检测到。体内小鼠牙胚中FRG 1蛋白定位于细胞质中，而体外mDE 6细胞中FRG 1主要在细胞核中检测到，少量在细胞质中检测到。骨形态发生蛋白4（BMP 4）处理的mDE 6细胞中，FRG 1蛋白表达在胞浆中增加，提示FRG 1可能易位到胞浆中。这些发现表明，FRG 1参与牙胚的形态发生，以及在釉质和牙本质基质的形成，FRG 1可能在BMP 4刺激后的小鼠牙发生中发挥作用。
Abnormal expression of Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is involved in the pathogenesis of FSHD. FRG1 is also important for the normal muscular and vascular development. Our previous study showed that FRG1 is one of the highly expressed genes in the mandible on embryonic day 10.5 (E10.5) than on E12.0. In this study, we investigated the temporospatial expression pattern of FRG1 mRNA and protein during the development of the mouse lower first molar, and also evaluated the subcellular localization of the FRG1 protein in mouse dental epithelial (mDE6) cells. The FRG1 expression was identified in the dental epithelial and mesenchymal cells at the initiation and bud stages. It was detected in the inner enamel epithelium at the cap and early bell stages. At the late bell and root formation stages, these signals were detected in ameloblasts and odontoblasts during the formation of enamel and dentin matrices, respectively. The FRG1 protein was localized in the cytoplasm in the mouse tooth germ in vivo, while FRG1 was detected predominantly in the nucleus and faintly in the cytoplasm in mDE6 cells in vitro. In mDE6 cells treated with bone morphogenetic protein 4 (BMP4), the protein expression of FRG1 increased in cytoplasm, suggesting that FRG1 may translocate to the cytoplasm. These findings suggest that FRG1 is involved in the morphogenesis of the tooth germ, as well as in the formation of enamel and dentin matrices and that FRG1 may play a role in the odontogenesis in the mouse following BMP4 stimulation.