Takamori K, Hosokawa R, Xu X, Deng X, Bringas P, Chai Y
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA.
J Dent Res. 2008 Mar;87(3):238-43. doi: 10.1177/154405910808700307.
The interaction between epithelial and mesenchymal tissues plays a critical role in the development of organs such as teeth, lungs, and hair. During tooth development, fibroblast growth factor (FGF) signaling is critical for regulating reciprocal epithelial and mesenchymal interactions. FGF signaling requires FGF ligands and their receptors (FGFRs). In this study, we investigated the role of epithelial FGF signaling in tooth development, using the Cre-loxp system to create tissue-specific inactivation of Fgfr1 in mice. In K14-Cre;Fgfr1(fl/fl) mice, the apical sides of enamel-secreting ameloblasts failed to adhere properly to each other, although ameloblast differentiation was unaffected at early stages. Prior to eruption, enamel structure was compromised in the K14-Cre;Fgfr1(fl/fl) mice and displayed severe enamel defects that mimic amelogenesis imperfecta (AI), with a rough, irregular enamel surface. These results suggest that there is a cell-autonomous requirement for FGF signaling in the dental epithelium during enamel formation. Loss of Fgfr1 affects ameloblast organization at the enamel-secretory stage and, hence, the formation of enamel.
上皮组织与间充质组织之间的相互作用在牙齿、肺和毛发等器官的发育中起着关键作用。在牙齿发育过程中，成纤维细胞生长因子（FGF）信号传导对于调节上皮与间充质之间的相互作用至关重要。FGF信号传导需要FGF配体及其受体（FGFRs）。在本研究中，我们利用Cre-loxp系统在小鼠中特异性敲除Fgfr1，以研究上皮FGF信号在牙齿发育中的作用。在K14-Cre;Fgfr1(fl/fl)小鼠中，分泌釉质的成釉细胞顶端未能正常相互黏附，尽管在早期阶段成釉细胞分化未受影响。在牙齿萌出前，K14-Cre;Fgfr1(fl/fl)小鼠的釉质结构受损，表现出严重的釉质缺陷，类似于釉质发育不全（AI），釉质表面粗糙、不规则。这些结果表明，在釉质形成过程中，牙齿上皮对FGF信号存在细胞自主需求。Fgfr1的缺失影响了釉质分泌阶段成釉细胞的组织排列，进而影响了釉质的形成。
