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Elucidation of molecular mechanisms on transition from crown to root in tooth development

阐明牙齿发育过程中从冠到根转变的分子机制

基本信息

批准号：
13470387
负责人：
HARADA Hidemitsu
金额：
$ 3.2万
依托单位：
OSAKA UNIVERSITY (2002-2003)Kyushu Dental College (2001)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

In development of human-teeth, mouse-and rat-molars, root formation with periodontal tissue starts after morphogenesis of crown is finished. However, the molecular mechanism for the transition from crown to root in the development has not been elucidated. Fibroblast growth factor (Fgf)-10, which is expressed in the dental mesenchyme, plays an important role in both cell-proliferation and differentiation of dental epithelium in the stage of crown morphogenesis. But, the expression of Fgf-10 disappears in the stage of root formation. On the other hand, in continuously growing teeth such as rodent incisor, vole-, rabbit-and gineapig-molar, the eternal formation of crown analog (labial side in case of incisors), which consists of enamel and dentin, resulting from the continuous expression of Fgf-10 at the apical end. To clarify significance of disappearance of Fgf-10 in the stage of root formation, we observed the growth of incisors of Fgf-10 deficient mice (lethal at postnatal 0 day) by implantation underneath the kidney capsule. In mutant type formation of enamel finished on the way of the development of incisors and only dentin continued to be formed. The incisors of Fgf-10 deficient mice mimicked the development of mouse-molars exactly. For example, Hertwig' epithelial sheath was observed not only in root analog of the lingual side but also in apical end of labial sides and both of the root sheath were fragmented concomitantly with the formation of root dentin. These results suggest that the disappearance of Fgf-10 is a key in formation of Hertwig' epithelial sheath and subsequently root formation with periodontal tissue.

在人类牙齿、小鼠和大鼠臼齿的发育过程中，牙冠形态发生完成后，牙根与牙周组织开始形成。然而，发育过程中从冠向根转变的分子机制尚未阐明。成纤维细胞生长因子（Fgf）-10在牙间充质中表达，在牙冠形态发生阶段的牙上皮细胞增殖和分化中发挥重要作用。但是，Fgf-10的表达在根形成阶段消失。另一方面，在啮齿动物门牙、田鼠、兔子和豚鼠磨牙等不断生长的牙齿中，由牙釉质和牙本质组成的牙冠类似物（门牙的唇侧）的永久形成，是由于根尖端持续表达Fgf-10所致。为了阐明根形成阶段 Fgf-10 消失的意义，我们通过植入肾囊下方观察 Fgf-10 缺陷小鼠（出生后 0 天致死）的门牙生长。在突变型中，牙釉质的形成在门牙发育的过程中完成，仅继续形成牙本质。 Fgf-10 缺陷小鼠的门牙完全模仿了小鼠臼齿的发育。例如，赫特维希上皮鞘不仅在舌侧的牙根类似物中观察到，而且在唇侧的根尖部也观察到，并且两个根鞘随着根牙本质的形成而破碎。这些结果表明，Fgf-10 的消失是 Hertwig 上皮鞘形成以及随后牙周组织牙根形成的关键。