Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ

Kan Saito, Frederic Michon, Aya Yamada, Hiroyuki Inuzuka, Satoko Yamaguchi, Emiko Fukumoto, Keigo Yoshizaki, Takashi Nakamura, Makiko Arakaki, Yuta Chiba, Masaki Ishikawa, Hideyuki Okano, Irma Thesleff, Satoshi Fukumoto

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number101329
JournaliScience
Volume23
Issue number7
DOIs
Publication statusPublished - Jul 24 2020

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ'. Together they form a unique fingerprint.

  • Cite this

    Saito, K., Michon, F., Yamada, A., Inuzuka, H., Yamaguchi, S., Fukumoto, E., Yoshizaki, K., Nakamura, T., Arakaki, M., Chiba, Y., Ishikawa, M., Okano, H., Thesleff, I., & Fukumoto, S. (2020). Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ. iScience, 23(7), [101329]. https://doi.org/10.1016/j.isci.2020.101329