Cessation of Fgf10 signaling, resulting in a defective dental epithelial stem cell compartment, leads to the transition from crown to root formation

Cessation of Fgf10 signaling, resulting in a defective dental epithelial stem cell compartment, leads to the transition from crown to root formation
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DOI:
10.1242/dev.02307
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发表时间:
2006-04-01
期刊:
影响因子:
4.6
通讯作者:
Harada, H
Harada, H
中科院分区:
生物学2区
文献类型:
--
作者:
Yokohama-Tamaki, T;Ohshima, H;Harada, H

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冠形成后,小鼠,大鼠和人类磨牙开始形成根。在这些牙齿中,成纤维细胞生长因子(FGF)10在从冠形成到根的过渡阶段消失。相比之下,由于FGF10的恒定表达形成和维护干细胞室,啮齿动物的切牙和VOLE磨牙表现出连续的生长。为了阐明根部形成与FGF10消失之间的关系,我们进行了两个实验,以实现FGF10功能的损失和增益。首先,我们检查了FGF10缺陷型小鼠门牙的产后生长,这些小鼠的缺陷在肾囊下植入后,被称为“顶芽”的牙皮上皮干细胞室。突变小鼠唇侧的生长模仿有限生长牙齿的发展。 5'-bromo-2'-脱氧尿苷(BRDU)标记和细胞角蛋白(CK)14和Notch2免疫染色表明,内部搪瓷上皮生长的抑制作用以及更活跃的外搪瓷上皮和/或静态性衰落的增生上皮根鞘形成。其次,我们检查了FGF10过表达在摩尔细菌过渡阶段的影响,这导致了涉及抑制其形成的顶端芽的形成。综上所述,这些结果表明,由于牙齿上皮干细胞室的丧失,FGF10信号传导的消失导致了从牙冠到根部形成的过渡。
Mouse, rat and human molars begin to form root after the completion of crown formation. In these teeth, fibroblast growth factor (Fgf) 10 disappears in the transitional stage from crown formation to root. By contrast, rodent incisors and vole molars demonstrate continuous growth, owing to the formation and maintenance of a stem cell compartment by the constant expression of Fgf10. To clarify the relationship between root formation and disappearance of Fgf10, we carried out two experiments for the loss and gain of Fgf10 function. First, we examined postnatal growth in the incisors of Fgf10-deficient mice, which have the defect of a dental epithelial stem cell compartment referred to as 'apical bud', after implantation under the kidney capsule. The growth at the labial side in the mutant mice mimics the development of limited-growth teeth. 5'-Bromo-2'-deoxyuridine (BrdU) labeling and cytokeratin (CK) 14 and Notch2 immunostaining suggested that the inhibition of inner enamel epithelium growth and the more-active proliferation of the outer enamel epithelium and/or stellate reticulum result in Hertwig's epithelial root sheath formation. Second, we examined the effects of Fgf10 overexpression in the transitional stage of molar germs, which led to the formation of apical bud involving in the inhibition of HERS formation. Taken together, these results suggest that the disappearance of Fgf10 signaling leads to the transition from crown to root formation, owing to the loss of a dental epithelial stem cell compartment.