The transcription factor Sox21 is expressed in the epithelium of developing teeth. The present study aimed to determine the role of Sox21 in tooth development. We found that disruption of Sox21 caused severe enamel hypoplasia, regional osteoporosis, and ectopic hair formation in the gingiva in Sox21 knockout incisors. Differentiation markers were lost in ameloblasts, which formed hair follicles expressing hair keratins. Molecular analysis and chromatin immunoprecipitation sequencing indicated that Sox21 regulated Anapc10, which recognizes substrates for ubiquitination-mediated degradation, and determined dental-epithelial versus hair follicle cell fate. Disruption of either Sox21 or Anapc10 induced Smad3 expression, accelerated TGF-β1-induced promotion of epithelial-to-mesenchymal transition (EMT), and resulted in E-cadherin degradation via Skp2. We conclude that Sox21 disruption in the dental epithelium leads to the formation of a unique microenvironment promoting hair formation and that Sox21 controls dental epithelial differentiation and enamel formation by inhibiting EMT via Anapc10.

转录因子Sox21在发育中的牙齿的上皮中表达。本研究旨在确定Sox21在牙齿发育中的作用。我们发现，Sox21的破坏会导致严重的牙釉质发育不全，区域性骨质疏松和Sox21剔除门牙的牙龈中异位毛发的形成。分化标记物在成釉细胞中丢失，形成成毛囊表达毛发角蛋白。分子分析和染色质免疫沉淀测序表明，Sox21调节了Anapc10，后者识别泛素介导的降解底物，并确定了牙齿上皮细胞与毛囊细胞的命运。Sox21或Anapc10的破坏诱导Smad3表达，加速TGF-β1诱导的上皮向间充质转化（EMT）的促进，并导致E-钙粘蛋白通过Skp2降解。