Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors
Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors
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DOI：
10.1242/dev.051672
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发表时间：
2010-11-15
期刊：
影响因子：
4.6
通讯作者：
Bellusci, Saverio
中科院分区：
文献类型：
--
作者：
Parsa, Sara;Kuremoto, Koh-ichi;Bellusci, Saverio
啮齿动物的门牙在整个生命过程中都会再生，这是因为牙齿近端存在上皮性干细胞和间充质干细胞。牙釉质是牙齿最坚硬的成分，由干细胞来源的成釉细胞专门在牙齿的唇部或外表面持续沉积。作为成釉细胞前体的上皮干细胞存在于门牙底部称为颈环的结构中。先前的研究表明，FGF10主要通过成纤维细胞生长因子受体2b(FGFR2b)发挥作用，对小鼠切牙上皮干细胞群体的发育至关重要。为了探索FGFR2b信号在发育和成年生活中的作用，我们使用了RTTA反式激活/四环素启动子方法，允许FGFR2b信号可诱导和可逆衰减。FGFR2b信号在胚胎期的下调导致唇颈环和内釉上皮层的异常发育。此外，出生后信号的减弱导致门牙生长受损，其特征是牙釉质形成失败和门牙退化。在细胞水平上，这些变化伴随着作为成釉细胞前体的运输放大细胞的增殖减少。信号阻断解除后，门牙恢复生长并重新形成釉质层，表明干细胞的存活没有受到出生后FGFR2b信号的短暂衰减的影响。综上所述，我们的结果表明，FGFR2b信号既调节着胚胎中门牙干细胞生态位的建立，也调节着成人门牙的再生能力。
Rodent incisors regenerate throughout the lifetime of the animal owing to the presence of epithelial and mesenchymal stem cells in the proximal region of the tooth. Enamel, the hardest component of the tooth, is continuously deposited by stem cell-derived ameloblasts exclusively on the labial, or outer, surface of the tooth. The epithelial stem cells that are the ameloblast progenitors reside in structures called cervical loops at the base of the incisors. Previous studies have suggested that FGF10, acting mainly through fibroblast growth factor receptor 2b (FGFR2b), is crucial for development of the epithelial stem cell population in mouse incisors. To explore the role of FGFR2b signaling during development and adult life, we used an rtTA transactivator/tetracycline promoter approach that allows inducible and reversible attenuation of FGFR2b signaling. Downregulation of FGFR2b signaling during embryonic stages led to abnormal development of the labial cervical loop and of the inner enamel epithelial layer. In addition, postnatal attenuation of signaling resulted in impaired incisor growth, characterized by failure of enamel formation and degradation of the incisors. At a cellular level, these changes were accompanied by decreased proliferation of the transit-amplifying cells that are progenitors of the ameloblasts. Upon release of the signaling blockade, the incisors resumed growth and reformed an enamel layer, demonstrating that survival of the stem cells was not compromised by transient postnatal attenuation of FGFR2b signaling. Taken together, our results demonstrate that FGFR2b signaling regulates both the establishment of the incisor stem cell niches in the embryo and the regenerative capacity of incisors in the adult.