Department of Craniofacial Development, Dental Institute, King's College London, Guy's Hospital, London, UK.
J Anat. 2011 May;218(5):534-43. doi: 10.1111/j.1469-7580.2011.01352.x. Epub 2011 Feb 21.
Fgf signalling is known to play critical roles in tooth development. Twenty-two Fgf ligands have been identified in mammals, but expression of only 10 in molars and three in the incisor loop stem cell region have been documented in murine tooth development. Our understanding of Fgf signalling in tooth development thus remains incomplete and we therefore carried out comparative in situ hybridisation analysis of unexamined Fgf ligands (eight in molars and 15 in cervical loops of incisors; Fgf11-Fgf14 were excluded from this analysis because they are not secreted and do not activate Fgf receptors) during tooth development. To identify where Fgf signalling is activated, we also examined the expression of Etv4 and Etv5, considered to be transcriptional targets of the Fgf signalling pathway. In molar tooth development, the expression of Fgf15 and Fgf20 was restricted to the primary enamel knots, whereas Etv4 and Etv5 were expressed in cells surrounding the primary enamel knots. Fgf20 expression was observed in the secondary enamel knots, whereas Fgf15 showed localised expression in the adjacent mesenchyme. Fgf16, Etv4 and Etv5 were strongly expressed in the ameloblasts of molars. In the incisor cervical loop stem cell region, Fgf17, Fgf18, Etv4 and Etv5 showed a restricted expression pattern. These molecules thus show dynamic temporo-spatial expression in murine tooth development. We also analysed teeth in Fgf15(-/-) and Fgf15(-/-) ;Fgf8(+/-) mutant mice. Neither mutant showed significant abnormalities in tooth development, indicating likely functional redundancy.
Fgf 信号通路在牙齿发育中起着至关重要的作用。在哺乳动物中已经鉴定出 22 种 Fgf 配体，但在鼠类牙齿发育中仅记录到 10 种在磨牙和 3 种在前切牙环干细胞区域表达。因此，我们对 Fgf 信号通路在牙齿发育中的作用的了解仍不完整，因此我们对未研究的 Fgf 配体（磨牙中的 8 种和切牙颈环中的 15 种；由于它们不分泌且不激活 Fgf 受体，因此未包括 Fgf11-Fgf14 进行了比较原位杂交分析）在牙齿发育过程中的表达进行了比较。为了确定 Fgf 信号通路的激活位置，我们还检查了 Etv4 和 Etv5 的表达，它们被认为是 Fgf 信号通路的转录靶标。在磨牙牙齿发育中，Fgf15 和 Fgf20 的表达仅限于初级釉质结，而 Etv4 和 Etv5 则在初级釉质结周围的细胞中表达。Fgf20 的表达在次级釉质结中观察到，而 Fgf15 在相邻的间质中表现出局部表达。Fgf16、Etv4 和 Etv5 在磨牙的成釉细胞中强烈表达。在前切牙颈环干细胞区域，Fgf17、Fgf18、Etv4 和 Etv5 表现出受限的表达模式。这些分子因此在鼠类牙齿发育中表现出动态的时空表达。我们还分析了 Fgf15(-/-) 和 Fgf15(-/-) ;Fgf8(+/-) 突变小鼠的牙齿。两种突变型在牙齿发育中均未显示出明显异常，表明可能存在功能冗余。
