Impaired Remodeling of Tight Junctions Associated with Loss of Enamel Rod Decussation in Tgfbr2(G357W/+) Mice

Tgfbr2(G357W/+)小鼠牙釉质棒交叉丧失与紧密连接重塑受损相关

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Abstract

During enamel secretion, ameloblasts follow a complex coordinated movement that results in the enamel rods being arranged in a crisscross pattern that contributes significantly to its exceptional mechanical properties. We previously determined that mutations in the gene encoding TGF-β receptor 2 (TGFR-2) in humans (TGFBR2) and mice (Tgfbr2) result in the formation of fully mineralized enamel that exhibits impaired decussation of enamel rods. Using Tgfbr2(G357W/+) mice, we demonstrated that this phenotype was due to disrupted coordinated movement of ameloblasts during enamel secretion. In this study, we used focused ion beam scanning electron microscopy (FIB-SEM) to look more closely at the area of the apical terminal web (ATW) where the cells are connected via tight junctions. We show that ameloblasts from wild-type littermates exhibit an abrupt shift in orientation at the ATW while Tgfbr2(G357W/+) mice show no signs of such shift. Moreover, ZO-1 distribution at the ATW was abnormal in Tgfbr2(G357W/+) mice with reduced accumulation at the ATW and presence of clusters of the protein at the basal side. These results suggest that abrupt orientation shift at the ATW via dynamic remodeling of tight junctions is essential for rows of ameloblasts to deposit enamel rods in opposite directions.

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