Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ.

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

doi:10.1016/j.isci.2020.101329

Kan Saito, Satoko Yamaguchi + Show 12 more

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https://doi.org/10.1016/j.isci.2020.101329

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Abstract

SummaryThe 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.

Highlights

Members of the SRY-Box (Sox) B group share a conserved eight-amino-acid group B homology domain located adjacent to the HMG domain
SUMMARY The transcription factor Sox21 is expressed in the epithelium of developing teeth
We found that disruption of Sox21 caused severe enamel hypoplasia, regional osteoporosis, and ectopic hair formation in the gingiva in Sox21 knockout incisors

Summary

Introduction

Members of the SRY-Box (Sox) B group share a conserved eight-amino-acid group B homology domain located adjacent to the HMG domain. The SoxB1 (Sox1–3) proteins function primarily as activators, whereas the closely related SoxB2 proteins (Sox and Sox21) are transcriptional repressors (Argenton et al, 2004; Sandberg et al, 2005). SoxB2 repression of SoxB1 expression was shown to promote neural differentiation in the central nervous system (CNS) and peripheral nervous system (Sandberg et al, 2005; Uchikawa et al, 1999). This repression is supported by the expression of Sox throughout the developing CNS and brain (Cunningham et al, 2008). The SoxB1 group proteins and their roles have received greater attention to date (Donner et al, 2007; Driskell et al, 2009; Groves and Bronner-Fraser, 2000) than SoxB2 group involvement in developmental processes

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