Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ
Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ
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DOI：
10.1016/j.isci.2020.101329
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发表时间：
2020-07-24
期刊：
影响因子：
5.8
通讯作者：
Fukumoto，Satoshi
中科院分区：
文献类型：
--
作者：
Saito，Kan;Michon，Frederic;Fukumoto，Satoshi
转录因子Sox 21在发育牙齿的上皮中表达。本研究旨在确定Sox 21在牙齿发育中的作用。我们发现，Sox 21的破坏引起严重的釉质发育不全，区域性骨质疏松症，和异位毛发形成的牙龈中的Sox 21敲除门牙。成釉细胞分化标志丢失，形成表达毛发角蛋白的毛囊。分子分析和染色质免疫沉淀测序表明，Sox 21调节Anapc 10，它识别底物的泛素化介导的降解，并确定牙上皮与毛囊细胞的命运。Sox 21或Anapc 10的破坏诱导Smad 3的表达，加速TGF-β1诱导的上皮向间充质转化（EMT）的促进，并导致E-cadherin通过Skp 2降解。我们的结论是，Sox 21破坏牙上皮导致形成一个独特的微环境，促进头发的形成和Sox 21控制牙上皮分化和釉质形成抑制EMT通过Anapc 10。
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.