Ellis-vanCreveld(EVC)综合征是一种常染色体隐性软骨发育不良。受影响的个体有一系列的骨骼缺陷,先天性心脏隔膜异常,面部中部缺陷,牙齿缺陷。先前使用Evc或Evc2突变小鼠的研究已经表征了导致各种类型的先天性缺陷的病理机制。一些EVC患者有多余的牙齿;然而,目前还不知道是否有多余的牙齿形成在Evc或Evc2突变小鼠,如果是,相关的病理机制是什么。在本研究中,我们使用Evc2突变小鼠,并分析了Evc2突变小鼠在不同阶段的磨牙模式。我们的研究表明,Evc2在牙齿间充质细胞内的功能丧失导致异常的磨牙模式,Evc2突变下颌骨中的最前磨牙代表一颗多余的牙齿。最后,我们提供的证据支持以下观点:Hedgehog信号受损和由于Evc2功能丧失而导致的WNT信号升高都有助于多余牙齿的形成。
Ellis-van Creveld (EVC) syndrome is an autosomal recessive chondrodysplasia. The affected individuals bear a series of skeleton defects, congenital heart septum anomalies, midfacial defects, and dental defects. Previous studies using Evc or
Evc2 mutant mice have characterized the pathological mechanism leading to various types of congenital defects. Some patients with EVC have supernumerary tooth; however, it is not known yet if there are supernumerary tooth formed in Evc or
Evc2 mutant mice, and if yes, what is the pathological mechanism associated. In the present study, we used
Evc2 mutant mice and analyze the pattern of molars in
Evc2 mutant mice at various stages. Our studies demonstrate that
Evc2 loss of function within the dental mesenchymal cells leads to abnormal molar patterning, and that the most anterior molar in the
Evc2 mutant mandible represents a supernumerary tooth. Finally, we provide evidence supporting the idea that both compromised Hedgehog signaling and elevated WNT signaling due to Evc2 loss of function contributes to the supernumerary tooth formation.