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

在人牙、鼠磨牙和大鼠磨牙的发育过程中，牙周组织的牙根形成是在牙冠形态发生完成后开始的。然而，在发育过程中，树冠向根部转变的分子机制尚未阐明。成纤维细胞生长因子-10表达于牙本质间充质中，在牙冠形态发生过程中对牙体上皮细胞的增殖和分化起重要作用。但在生根阶段，成纤维细胞生长因子-10的表达消失。另一方面，在啮齿动物的切牙、田鼠、兔和小鼠的磨牙等持续生长的牙齿中，由于在根尖末端持续表达着成纤维细胞生长因子-10，形成了恒定的牙冠类似物(如门牙的唇侧)，它由釉质和牙本质组成。为了阐明成纤维细胞生长因子-10的消失在牙根形成过程中的意义，我们观察了成纤维细胞生长因子-10缺陷小鼠(出生后第0天死亡)在肾被膜下植入后切牙的生长情况。在突变型中，釉质的形成在门牙发育的过程中完成，只有牙本质继续形成。成纤维细胞生长因子-10基因缺陷小鼠的门牙与小鼠磨牙的发育完全一致。例如，Hertwig上皮鞘不仅见于舌侧的根部，也见于唇侧的顶端，两个根鞘都随着根牙本质的形成而碎裂。这些结果提示，在Hertwig上皮鞘的形成和牙周组织的牙根形成过程中，成纤维细胞生长因子-10的消失是关键。

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.