Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ

iScience

Frederic Michon¹  Hiroyuki Inuzuka²  Emiko Fukumoto³  Satoshi Fukumoto⁴  Aya Yamada⁵  Yuta Chiba⁶  Irma Thesleff⁷  Masaki Ishikawa⁸  Satoko Yamaguchi⁸  Kan Saito⁸  Hideyuki Okano⁸  Keigo Yoshizaki⁸  Takashi Nakamura⁸  Makiko Arakaki⁹ 

[1] Corresponding author;Institute for Neurosciences of Montpellier, Inserm U1051, University of Montpellier, 34295 Montpellier, France;Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan;Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;Developmental Biology Program, Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland;Division of Molecular Pharmacology and Cell Biophysics, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan;Division of Operative Dentistry, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan;Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan;Section of Orthodontics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan;

关键词: Rodent Dentistry;    Developmental Genetics;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown