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小型猪乳切牙形态发生和牙发生中涉及 FGF 信号的关键基因的时空表达模式。

Spatiotemporal Expression Patterns of Critical Genes Involved in FGF Signaling During Morphogenesis and Odontogenesis of Deciduous Molars in Miniature Pigs.

机构信息

Beijing Laboratory of Oral Health; Capital Medical University School of Stomatology, Beijing, China.

Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.

出版信息

Int J Med Sci. 2022 Jan 1;19(1):132-141. doi: 10.7150/ijms.61798. eCollection 2022.

Abstract

The fibroblast growth factor (FGF) pathway plays an important role in epithelial-mesenchymal interactions during tooth development. Nevertheless, how the ligands, receptors, and antagonists of the FGF pathway are involved in epithelial-mesenchymal interactions remains largely unknown. Miniature pigs exhibit tooth anatomy and replacement patterns like those in humans and hence can serve as large animal models. The present study investigated the spatiotemporal expression patterns of critical genes encoding FGF ligands (, , , and ), antagonists ( and ) and receptors (, , and ) in the third deciduous molars of miniature pigs at the cap (embryonic day 40, E40), early bell (E50), and late bell (E60) stages. The results of hybridization (ISH) with tyramide signal amplification and of qRT-PCR analysis revealed increased expression of , , , and in dental epithelium and of and in mesenchyme from E40 to E50. In contrast, the results revealed decreased expression of , , , and in dental epithelium and of , , , and in the mesenchyme from E40 to E60. Mesenchyme signals of , , , , , and were concentrated in the odontoblast layer from E50 to E60. The distinct expression patterns of these molecules indicated elaborate regulation during dental morphogenesis. Our results provide a foundation for further investigation into fine-tuning dental morphogenesis and odontogenesis by controlling interactions between dental epithelium and mesenchyme, thus promoting tooth regeneration in large mammals.

摘要

成纤维细胞生长因子(FGF)途径在牙齿发育过程中的上皮-间充质相互作用中发挥重要作用。然而,FGF 途径的配体、受体和拮抗剂如何参与上皮-间充质相互作用在很大程度上仍不清楚。小型猪表现出与人类相似的牙齿解剖结构和替换模式,因此可以作为大型动物模型。本研究在小型猪第三恒磨牙的帽状期(胚胎第 40 天,E40)、早期钟状期(E50)和晚期钟状期(E60),调查了编码 FGF 配体(、、、)、拮抗剂(和)以及受体(、、和)的关键基因在第三恒磨牙中的时空表达模式。采用原位杂交(ISH)与辣根过氧化物酶信号放大和 qRT-PCR 分析的结果显示,在 E40 到 E50 期间,牙上皮中 、、和 的表达增加,而间质中 、和 的表达增加。相比之下,E40 到 E60 期间,牙上皮中 、、和 的表达减少,而间质中 、、和 的表达减少。E50 到 E60 期间,间充质中 、、、、和 的信号集中在成牙本质细胞层。这些分子的独特表达模式表明,在牙齿形态发生过程中存在精细的调控。我们的研究结果为进一步研究通过控制牙上皮和间充质之间的相互作用来精细调节牙齿形态发生和牙发生,从而促进大型哺乳动物的牙齿再生提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8d6/8692127/42d9ed700d45/ijmsv19p0132g001.jpg

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