FGF8 and BMP2 mediated dynamic regulation of dental mesenchyme proliferation and differentiation via Lhx8/Suv39h1 complex.
FGF8 and BMP2 mediated dynamic regulation of dental mesenchyme proliferation and differentiation via Lhx8/Suv39h1 complex.
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FGF8和BMP2通过Lhx8/SUV39H1复合体介导牙间充质增殖和分化的动态调节。
DOI：
10.1111/jcmm.16351
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Zhou C;Chen D;Ren J;Huang D;Li R;Luo H;Guan C;Cao Y;Wang W
同源异型盒基因LIM-Homeobox 8(Lhx8)是牙齿间充质发育所必需的转录因子。然而，Lhx8本身是如何被调控和调控牙齿发育的仍然知之甚少。在这项研究中，我们使用RNAScope方法检测了Lhx8和SUV39H1在牙间充质中的共表达模式，这与早期上皮信号成纤维细胞生长因子8(FGF8)和晚期间充质信号骨形态发生蛋白2(BMP2)的动态表达谱相吻合。此外，FGF8激活Lhx8，而BMP2在转录水平抑制Lhx8的表达。Lhx8在早期牙间充质中的高表达通过与SUV39H1相互作用而维持细胞的未分化状态。SUV39H1是一种组蛋白赖氨酸N-甲基转移酶，在牙间充质中组成性表达。此外，在体外器官培养模型中，SUV39H1基因的敲除显著阻断了Lhx8和FGF8的功能。在机制上，Lhx8/SUV39H1识别成牙本质细胞分化相关基因，并通过其启动子上的H3K9甲基化抑制基因表达。综上所述，我们的数据表明Lhx8/SUV39H1复合体受上皮-间充质信号的反向调节，通过H3K9甲基化平衡牙间充质的分化和增殖。
The homeobox gene, LIM‐homeobox 8 (Lhx8), has previously been identified as an essential transcription factor for dental mesenchymal development. However, how Lhx8 itself is regulated and regulates odontogenesis remains poorly understood. In this study, we employed an RNAscope assay to detect the co‐expression pattern of Lhx8 and Suv39h1 in the dental mesenchyme, which coincided with the dynamic expression profiles of the early epithelium signal of Fibroblast Growth Factor 8 (FGF8) and the later mesenchymal signal Bone Morphogenetic Protein 2 (BMP2). Moreover, FGF8 activated Lhx8, whereas BMP2 repressed Lhx8 expression at the transcriptional level. The high expression of Lhx8 in the early dental mesenchyme maintained the cell fate in an undifferentiated status by interacting with Suv39h1, a histone‐lysine N‐methyltransferase constitutively expressed in the dental mesenchyme. Further in the ex vivo organ culture model, the knockdown of Suv39h1 significantly blocked the function of Lhx8 and FGF8. Mechanistically, Lhx8/Suv39h1 recognized the odontoblast differentiation‐related genes and repressed gene expression via methylating H3K9 on their promoters. Taken together, our data here suggest that Lhx8/Suv39h1 complex is inversely regulated by epithelium‐mesenchymal signals, balancing the differentiation and proliferation of dental mesenchyme via H3K9 methylation.
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影响因子：
2.7
作者：
Laurikkala, J;Kassai, Y;Itoh, N
通讯作者：
Itoh, N
DOI：
10.1007/978-1-61779-860-3_14
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Oshima, Masamitsu;Ogawa, Miho;Tsuji, Takashi
通讯作者：
Tsuji, Takashi
影响因子：
48
作者：
Nakao, Kazuhisa;Morita, Ritsuko;Tsuji, Takashi
通讯作者：
Tsuji, Takashi
影响因子：
2.7
作者：
Denaxa, Myrto;Sharpe, Paul T.;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis
影响因子：
4.6
作者：
Jia, Shihai;Zhou, Jing;Jiang, Rulang
通讯作者：
Jiang, Rulang