Journal article
Pitx2-Sox2-Lef1 interactions specify progenitor oral/dental epithelial cell signaling centers
Development (Cambridge), Vol.147(11), dev186023
06/01/2020
DOI: 10.1242/dev.186023
PMCID: PMC7286298
PMID: 32439755
Abstract
Epithelial signaling centers control epithelial invagination and organ development, but how these centers are specified remains unclear. We report that Pitx2 (the first transcriptional marker for tooth development) controls the embryonic formation and patterning of epithelial signaling centers during incisor development. We demonstrate using Krt(14Cre)/Pitx2(flox/flox) (Pitx2(cKO)) and Rosa26(CreERT)/Pitx2(flox/flox) mice that loss of Pitx2 delays epithelial invagination, and decreases progenitor cell proliferation and dental epithelium cell differentiation. Developmentally, Pitx2 regulates formation of the Sox2(+) labial cervical loop (LaCL) stem cell niche in concert with two signaling centers: the initiation knot and enamel knot. The loss of Pitx2 disrupted the patterning of these two signaling centers, resulting in tooth arrest at E14.5. Mechanistically, Pitx2 transcriptional activity and DNA binding is inhibited by Sox2, and this interaction controls gene expression in specific Sox2 and Pitx2 co-expression progenitor cell domains. We demonstrate new transcriptional mechanisms regulating signaling centers by Pitx2, Sox2, Lef1 and Irx1.
Details
- Title: Subtitle
- Pitx2-Sox2-Lef1 interactions specify progenitor oral/dental epithelial cell signaling centers
- Creators
- Wenjie Yu - University of IowaZhao Sun - University of IowaYan Sweat - University of IowaMason Sweat - University of IowaShankar Rengasamy Venugopalan - University of IowaSteven Eliason - University of IowaHuojun Cao - University of IowaMichael L. Paine - University of Southern CaliforniaBrad A. Amendt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.147(11), dev186023
- DOI
- 10.1242/dev.186023
- PMID
- 32439755
- PMCID
- PMC7286298
- NLM abbreviation
- Development
- ISSN
- 0950-1991
- eISSN
- 1477-9129
- Publisher
- Company Biologists Ltd
- Number of pages
- 13
- Grant note
- DE13941; EB025873; DE025328; DE026433; T90 DE024296 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA College of Dentistry of The University of Iowa Carver College of Medicine of The University of Iowa
- Language
- English
- Date published
- 06/01/2020
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Endodontics; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984284348402771
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