Xiaoyan Chen, Jing Liu, Nan Li, Yu Wang, Nan Zhou, Lei Zhu, Yiding Shi, Yingzhang Wu, Jing Xiao, Chao Liu
{"title":"牙上皮间充质Wnt/β-catenin信号传导诱导Wnt和BMP拮抗剂。","authors":"Xiaoyan Chen, Jing Liu, Nan Li, Yu Wang, Nan Zhou, Lei Zhu, Yiding Shi, Yingzhang Wu, Jing Xiao, Chao Liu","doi":"10.1080/15476278.2019.1633871","DOIUrl":null,"url":null,"abstract":"<p><p>Previous studies indicated that the elevated mesenchymal Wnt/β-catenin signaling deprived dental mesenchyme of odontogenic fate. By utilizing <i>ex vivo</i> or pharmacological approaches, Wnt/β-catenin signaling in the developing dental mesenchyme was suggested to suppress the odontogenic fate by disrupting the balance between Axin2 and Runx2. In our study, the <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> mouse was used to explore how mesenchymal Wnt/β-catenin signaling suppressed the odontogenic fate <i>in vivo</i>. We found that all of the incisor and half of the molar germs of <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i>mice started to regress at E14.5 and almost disappeared at birth. The expression of <i>Fgf3</i> and <i>Msx1</i> was dramatically down-regulated in the E14.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> incisor and molar mesenchyme, while <i>Runx2</i>transcription was only diminished in incisor mesenchyme. Intriguingly, in the E14.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> incisor epithelium, the expression of <i>Noggin</i> was activated, while <i>Shh</i> was abrogated. Similarly, the Wnt and BMP antagonists, <i>Ectodin</i> and <i>Noggin</i> were also ectopically activated in the E14.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> molar epithelium. Recombination of E13.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> molar mesenchyme with E10.5 and E13.5 WT dental epithelia failed to develop tooth. Taken together, the mesenchymal Wnt/β-catenin signaling resulted in the loss of odontogenic fate <i>in vivo</i> not only by directly suppressing odontogenic genes expression but also by inducing Wnt and BMP antagonists in dental epithelium.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15476278.2019.1633871","citationCount":"7","resultStr":"{\"title\":\"Mesenchymal Wnt/β-catenin signaling induces Wnt and BMP antagonists in dental epithelium.\",\"authors\":\"Xiaoyan Chen, Jing Liu, Nan Li, Yu Wang, Nan Zhou, Lei Zhu, Yiding Shi, Yingzhang Wu, Jing Xiao, Chao Liu\",\"doi\":\"10.1080/15476278.2019.1633871\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Previous studies indicated that the elevated mesenchymal Wnt/β-catenin signaling deprived dental mesenchyme of odontogenic fate. By utilizing <i>ex vivo</i> or pharmacological approaches, Wnt/β-catenin signaling in the developing dental mesenchyme was suggested to suppress the odontogenic fate by disrupting the balance between Axin2 and Runx2. In our study, the <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> mouse was used to explore how mesenchymal Wnt/β-catenin signaling suppressed the odontogenic fate <i>in vivo</i>. We found that all of the incisor and half of the molar germs of <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i>mice started to regress at E14.5 and almost disappeared at birth. The expression of <i>Fgf3</i> and <i>Msx1</i> was dramatically down-regulated in the E14.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> incisor and molar mesenchyme, while <i>Runx2</i>transcription was only diminished in incisor mesenchyme. Intriguingly, in the E14.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> incisor epithelium, the expression of <i>Noggin</i> was activated, while <i>Shh</i> was abrogated. Similarly, the Wnt and BMP antagonists, <i>Ectodin</i> and <i>Noggin</i> were also ectopically activated in the E14.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> molar epithelium. Recombination of E13.5 <i>Osr2-cre<sup>KI</sup>; Ctnnb1<sup>ex3f</sup></i> molar mesenchyme with E10.5 and E13.5 WT dental epithelia failed to develop tooth. 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Mesenchymal Wnt/β-catenin signaling induces Wnt and BMP antagonists in dental epithelium.
Previous studies indicated that the elevated mesenchymal Wnt/β-catenin signaling deprived dental mesenchyme of odontogenic fate. By utilizing ex vivo or pharmacological approaches, Wnt/β-catenin signaling in the developing dental mesenchyme was suggested to suppress the odontogenic fate by disrupting the balance between Axin2 and Runx2. In our study, the Osr2-creKI; Ctnnb1ex3f mouse was used to explore how mesenchymal Wnt/β-catenin signaling suppressed the odontogenic fate in vivo. We found that all of the incisor and half of the molar germs of Osr2-creKI; Ctnnb1ex3fmice started to regress at E14.5 and almost disappeared at birth. The expression of Fgf3 and Msx1 was dramatically down-regulated in the E14.5 Osr2-creKI; Ctnnb1ex3f incisor and molar mesenchyme, while Runx2transcription was only diminished in incisor mesenchyme. Intriguingly, in the E14.5 Osr2-creKI; Ctnnb1ex3f incisor epithelium, the expression of Noggin was activated, while Shh was abrogated. Similarly, the Wnt and BMP antagonists, Ectodin and Noggin were also ectopically activated in the E14.5 Osr2-creKI; Ctnnb1ex3f molar epithelium. Recombination of E13.5 Osr2-creKI; Ctnnb1ex3f molar mesenchyme with E10.5 and E13.5 WT dental epithelia failed to develop tooth. Taken together, the mesenchymal Wnt/β-catenin signaling resulted in the loss of odontogenic fate in vivo not only by directly suppressing odontogenic genes expression but also by inducing Wnt and BMP antagonists in dental epithelium.
期刊介绍:
Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes.
The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering.
The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.