Journal article
The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation
Development (Cambridge), Vol.140(16), pp.3348-3359
08/2013
DOI: 10.1242/dev.089193
PMCID: PMC3737717
PMID: 23863486
Abstract
The mouse incisor is a remarkable tooth that grows throughout the animal's lifetime. This continuous renewal is fueled by adult epithelial stem cells that give rise to ameloblasts, which generate enamel, and little is known about the function of microRNAs in this process. Here, we describe the role of a novel Pitx2:miR-200c/141:noggin regulatory pathway in dental epithelial cell differentiation. miR-200c repressed noggin, an antagonist of Bmp signaling. Pitx2 expression caused an upregulation of miR-200c and chromatin immunoprecipitation assays revealed endogenous Pitx2 binding to the miR-200c/141 promoter. A positive-feedback loop was discovered between miR-200c and Bmp signaling. miR-200c/141 induced expression of E-cadherin and the dental epithelial cell differentiation marker amelogenin. In addition, miR-203 expression was activated by endogenous Pitx2 and targeted the Bmp antagonist Bmper to further regulate Bmp signaling. miR-200c/141 knockout mice showed defects in enamel formation, with decreased E-cadherin and amelogenin expression and increased noggin expression. Our in vivo and in vitro studies reveal a multistep transcriptional program involving the Pitx2:miR-200c/141:noggin regulatory pathway that is important in epithelial cell differentiation and tooth development.
Details
- Title: Subtitle
- The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation
- Creators
- Huojun Cao - Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA 52242, USAAndrew JheonXiao LiZhao SunJianbo WangSergio FlorezZichao ZhangMichael T McManusOphir D KleinBrad A Amendt
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.140(16), pp.3348-3359
- DOI
- 10.1242/dev.089193
- PMID
- 23863486
- PMCID
- PMC3737717
- NLM abbreviation
- Development
- ISSN
- 0950-1991
- eISSN
- 1477-9129
- Publisher
- England
- Grant note
- R01 DE013941 / NIDCR NIH HHS S10 RR026645 / NCRR NIH HHS S10RR026645 / NCRR NIH HHS K99-DE022059 / NIDCR NIH HHS K99 DE022059 / NIDCR NIH HHS DE021420 / NIDCR NIH HHS R00 DE022059 / NIDCR NIH HHS R01 DE021420 / NIDCR NIH HHS
- Language
- English
- Date published
- 08/2013
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Endodontics; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025416802771
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