Dong Xiuqing, Shen Bin, Ruan Ningsheng, Guan Zhen, Zhang Yanding, Chen YiPing, Hu Xuefeng
Center for Biomedicine Research of South China, Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Science, Fujian Normal University, Fuzhou, 350108, Fujian, People's Republic of China.
Histochem Cell Biol. 2014 Dec;142(6):657-65. doi: 10.1007/s00418-014-1241-y. Epub 2014 Jul 4.
The developing murine tooth has been used as an excellent model system to study the molecular mechanism of organ development and regeneration. While the expression patterns of numerous regulatory genes have been examined and their roles have begun to be revealed in the developing murine tooth, little is known about gene expression and function in human tooth development. In order to unveil the molecular mechanisms that regulate human tooth morphogenesis, we examined the expression patterns of the major BMP signaling pathway molecules in the developing human tooth germ at the cap and bell stages by in situ hybridization, immunohistochemistry, and real-time RT-PCR. Expression of BMP ligands and antagonist, including BMP2, BMP3, BMP4, BMP7, and NOOGGIN, exhibited uniform patterns in the tooth germs of incisor and molar at the cap and bell stages with stronger expression in the inner dental epithelium than that in the dental mesenchyme. Both type I and type II BMP receptors were present in widespread expression pattern in the whole-enamel organ and the dental mesenchyme with the strongest expression in inner dental epithelium at the cap and bell stages. SMAD4 and SMAD1/5/8 showed an expression pattern similar to that of BMP ligands with more intensive signals in the inner dental epithelium. Despite some unique and distinct patterns as compared to the mouse, the intensive expression of BMP signaling pathway molecules in the developing human tooth strongly suggests conserved functions of BMP signaling during human odontogenesis, such as in mediating tissue interactions and regulating differentiation and organization of odontogenic tissues. Our results provide an important set of documents for studying molecular regulatory mechanisms underlying tooth development and regeneration in humans.
发育中的小鼠牙齿已被用作研究器官发育和再生分子机制的优秀模型系统。虽然已经研究了许多调控基因的表达模式,并且它们在发育中的小鼠牙齿中的作用也已开始显现,但对于人类牙齿发育中的基因表达和功能却知之甚少。为了揭示调控人类牙齿形态发生的分子机制,我们通过原位杂交、免疫组织化学和实时逆转录聚合酶链反应,研究了帽状期和钟状期发育中的人类牙胚中主要骨形态发生蛋白(BMP)信号通路分子的表达模式。BMP配体和拮抗剂,包括BMP2、BMP3、BMP4、BMP7和头蛋白(NOOGGIN),在帽状期和钟状期切牙和磨牙的牙胚中呈现均匀的表达模式,在内釉上皮中的表达强于牙间充质。I型和II型BMP受体在整个釉器和牙间充质中广泛表达,在帽状期和钟状期内釉上皮中的表达最强。SMAD4和SMAD1/5/8的表达模式与BMP配体相似,在内釉上皮中的信号更强。尽管与小鼠相比存在一些独特和明显的模式,但BMP信号通路分子在发育中的人类牙齿中的强烈表达强烈表明,BMP信号在人类牙齿发生过程中具有保守功能,例如介导组织相互作用以及调节牙源性组织的分化和组织。我们的研究结果为研究人类牙齿发育和再生的分子调控机制提供了重要的资料。
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