Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development

Shahad Al Thamin, Yuta Chiba, Keigo Yoshizaki, Tian Tian, Ling Ling Jia, Xin Wang, Kan Saito, Jiyao Li, Aya Yamada, Satoshi Fukumoto

研究成果: Contribution to journalArticle査読

抄録

The epithelial-mesenchymal interactions are essential for the initiation and regulation of the development of teeth. Following the initiation of tooth development, numerous growth factors are secreted by the dental epithelium and mesenchyme that play critical roles in cellular differentiation. During tooth morphogenesis, the dental epithelial stem cells differentiate into several cell types, including inner enamel epithelial cells, which then differentiate into enamel matrix-secreting ameloblasts. Recently, we reported that the novel basic-helix-loop-helix transcription factor, AmeloD, is actively engaged in the development of teeth as a regulator of dental epithelial cell motility. However, the gene regulation mechanism of AmeloD is still unknown. In this study, we aimed to uncover the mechanisms regulating AmeloD expression during tooth development. By screening growth factors that are important in the early stages of tooth formation, we found that TGF-β1 induced AmeloD expression and ameloblast differentiation in the dental epithelial cell line, SF2. TGF-β1 phosphorylated ERK1/2 and Smad2/3 to induce AmeloD expression, whereas treatment with the MEK inhibitor, U0126, inhibited AmeloD induction. Promoter analysis of AmeloD revealed that the proximal promoter of AmeloD showed high activity in dental epithelial cell lines, which was enhanced following TGF-β1 stimulation. These results suggested that TGF-β1 activates AmeloD transcription via ERK1/2 phosphorylation. Our findings provide new insights into the mechanisms that govern tooth development.

本文言語英語
ジャーナルJournal of cellular physiology
DOI
出版ステータス受理済み/印刷中 - 2021

All Science Journal Classification (ASJC) codes

  • 生理学
  • 臨床生化学
  • 細胞生物学

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