Kettunen P, Karavanova I, Thesleff I
Developmental Biology Programme, University of Helsinki, Finland.
Dev Genet. 1998;22(4):374-85. doi: 10.1002/(SICI)1520-6408(1998)22:4<374::AID-DVG7>3.0.CO;2-3.
To elucidate the roles of fibroblast growth factors (FGF) in tooth development, we have analyzed the expression patterns of fibroblast growth factor receptors (FGFR) in mouse teeth by in situ hybridization and studied the effects of FGF-2, -4, -8, and -9 on cell proliferation in vitro by local application with beads on isolated dental mesenchymes. mRNAs of FGFR-1, -2, and -3 were localized by probes specific for the alternative splice variants IIIb and IIIc. The expression patterns of FGFR1 -2, and -3 were completely different, and the two splicing variants of FGFR1 and 2 exhibited different expression domains. FGFR4 was not expressed in the developing teeth. The IIIb splice forms of FGFR1 and -2 were expressed in the dental epithelium during morphogenesis. The IIIc splice form of FGFR1 was expressed both in epithelium and mesenchyme whereas FGFR2 IIIc was confined to the mesenchymal cells of the dental follicle. Both splice forms of FGFR3 were expressed in dental papilla mesenchyme. None of the FGF-receptors was detected in the primary enamel knot, the putative signaling center regulating tooth morphogenesis. This may explain the fact that enamel knot cells do not proliferate, although they express intensely mitogenic FGFs. Beads releasing FGF-2, -4, -8, or -9 proteins stimulated cell proliferation in cultured dental mesenchymes. These data, together with our earlier data on FGF expression [Kettunen and Thesleff (1998): Dev Dyn 211:256-268] suggest that FGF-8 and -9 mediate epithelial-mesenchymal interactions during tooth initiation. During advancing morphogenesis FGF-3, -4, and -9 may act both on mesenchyme and epithelium. Finally, the intense expression of FGFR1 in odontoblasts and ameloblasts and FGFR2 IIIb in ameloblasts suggests that FGFs participate in regulation of their differentiation and/or secretory functions.
为阐明成纤维细胞生长因子（FGF）在牙齿发育中的作用，我们通过原位杂交分析了小鼠牙齿中纤维母细胞生长因子受体（FGFR）的表达模式，并通过在分离的牙间充质上局部应用珠子来研究FGF-2、-4、-8和-9对体外细胞增殖的影响。通过针对选择性剪接变体IIIb和IIIc的特异性探针来定位FGFR-1、-2和-3的mRNA。FGFR1、-2和-3的表达模式完全不同，并且FGFR1和2的两种剪接变体表现出不同的表达域。FGFR4在发育中的牙齿中不表达。FGFR1和-2的IIIb剪接形式在形态发生过程中在牙上皮中表达。FGFR1的IIIc剪接形式在上皮和间充质中均有表达，而FGFR2 IIIc则局限于牙囊的间充质细胞。FGFR3的两种剪接形式均在牙乳头间充质中表达。在初级釉结（推测为调节牙齿形态发生的信号中心）中未检测到任何FGF受体。这可能解释了尽管釉结细胞强烈表达促有丝分裂的FGF，但它们却不增殖这一事实。释放FGF-2、-4、-8或-9蛋白的珠子刺激了培养的牙间充质中的细胞增殖。这些数据，连同我们早期关于FGF表达的数据[Kettunen和Thesleff（1998）：《发育动力学》211：256 - 268]表明，FGF-8和-9在牙齿起始过程中介导上皮-间充质相互作用。在形态发生推进过程中，FGF-3、-4和-9可能同时作用于间充质和上皮。最后，FGFR1在成牙本质细胞和成釉细胞中的强烈表达以及FGFR2 IIIb在成釉细胞中的强烈表达表明FGF参与调节它们的分化和/或分泌功能。
