journal article Oct 14, 2014

Mesenchymal TGF-βSignaling Orchestrates Dental Epithelial Stem Cell Homeostasis Through Wnt Signaling

Stem Cells Vol. 32 No. 11 pp. 2939-2948 · Oxford University Press (OUP)
View at Publisher Save 10.1002/stem.1772
Abstract
AbstractIn mouse, continuous growth of the postnatal incisor is coordinated by two populations of multipotent progenitor cells, the dental papilla mesenchymal cells and dental epithelial stem cells, residing at the proximal end of the incisor, yet the molecular mechanism underlying the cooperation between mesenchymal and epithelial cells is largely unknown. Here, transforming growth factor-β (TGF-β) type II receptor (Tgfbr2) was specifically deleted within the postnatal dental papilla mesenchyme. The Tgfbr2-deficient mice displayed malformed incisors with wavy mineralized structures at the labial side as a result of increased differentiation of dental epithelial stem cells. We found that mesenchymal Tgfbr2 disruption led to upregulated expression of Wnt5a and downregulated expression of Fgf3/10 in the mesenchyme, both of which synergistically enhanced Lrp5/6-β-catenin signaling in the cervical loop epithelium. In accord with these findings, mesenchyme-specific depletion of the Wnt transporter gene Wls abolished the aberrant mineralized structures caused by Tgfbr2 deletion. Thus, mesenchymal TGF-β signaling provides a unifying mechanism for the homeostasis of dental epithelial stem cells via a Wnt signaling-mediated mesenchymal-epithelial cell interaction. Stem Cells  2014;32:2939–2948
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References
30
[1]
Mitsiadis "Stem cell niches in mammals" Exp Cell Res (2007) 10.1016/j.yexcr.2007.07.027
[2]
Thesleff "Regulation of epithelial stem cells in tooth regeneration" C R Biol (2007) 10.1016/j.crvi.2007.03.005
[3]
Wang "An integrated gene regulatory network controls stem cell proliferation in teeth" PLoS Biol (2007) 10.1371/journal.pbio.0050159
[4]
Seidel "Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor" Development (2010) 10.1242/dev.056358
[5]
Nusse "Wnt signaling and stem cell control" Cell Res (2008) 10.1038/cr.2008.47
[6]
Suomalainen "Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells" Dev Dyn (2010) 10.1002/dvdy.22106
[7]
Jarvinen "Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling" Proc Natl Acad Sci USA (2006) 10.1073/pnas.0607289103
[8]
Liu "beta-Catenin initiates tooth neogenesis in adult rodent incisors" J Dent Res (2010) 10.1177/0022034510370090
[9]
Wang "Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood" Development (2009) 10.1242/dev.033803
[10]
Ito "Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects" Development (2003) 10.1242/dev.00708
[11]
Ko "Smad4 is required to regulate the fate of cranial neural crest cells" Dev Biol (2007) 10.1016/j.ydbio.2007.09.050
[12]
Li "SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis" Development (2011) 10.1242/dev.061341
[13]
Xu "Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-beta/BMP signaling during tooth and palate development" Dev Cell (2008) 10.1016/j.devcel.2008.06.004
[14]
Zhao "Alk5-mediated transforming growth factor beta signaling acts upstream of fibroblast growth factor 10 to regulate the proliferation and maintenance of dental epithelial stem cells" Mol Cell Biol (2011) 10.1128/mcb.01439-10
[15]
Zhao "TGF-beta type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner" Dev Biol (2008) 10.1016/j.ydbio.2008.03.045
[16]
Oshimori "The harmonies played by TGF-beta in stem cell biology" Cell Stem Cell (2012) 10.1016/j.stem.2012.11.001
[17]
Gao "Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice" Mol Cell Biol (2009) 10.1128/mcb.00706-09
[18]
Tan "Smad4 is required for maintaining normal murine postnatal bone homeostasis" J Cell Sci (2007) 10.1242/jcs.03466
[19]
Zha "Collagen1alpha1 promoter drives the expression of Cre recombinase in osteoblasts of transgenic mice" J Genet Genomics (2008) 10.1016/s1673-8527(08)60072-7
[20]
Chytil "Conditional inactivation of the TGF-beta type II receptor using Cre:Lox" Genesis (2002) 10.1002/gene.10046
[21]
Huang "Wls is expressed in the epidermis and regulates embryonic hair follicle induction in mice" PLoS One (2012) 10.1371/journal.pone.0045904
[22]
Sun "Expression of dentin sialoprotein (DSP) and other molecular determinants by a new cell line from dental papillae, MDPC-23" Connect Tissue Res (1998) 10.3109/03008209809002443
[23]
Moorman "Sensitive nonradioactive detection of mRNA in tissue sections: Novel application of the whole-mount in situ hybridization protocol" J Histochem Cytochem (2001) 10.1177/002215540104900101
[24]
Juuri "Sox2 marks epithelial competence to generate teeth in mammals and reptiles" Development (2013) 10.1242/dev.089599
[25]
Mikels "Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context" PLoS Biol (2006) 10.1371/journal.pbio.0040115
[26]
Verkaar "A model for signaling specificity of Wnt/Frizzled combinations through co-receptor recruitment" FEBS Lett (2010) 10.1016/j.febslet.2010.08.030
[27]
Banziger "Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells" Cell (2006) 10.1016/j.cell.2006.02.049
[28]
Bartscherer "Secretion of Wnt ligands requires Evi, a conserved transmembrane protein" Cell (2006) 10.1016/j.cell.2006.04.009
[29]
Carpenter "Generation of mice with a conditional null allele for Wntless" Genesis (2010) 10.1002/dvg.20651
[30]
Yang "Cessation of epithelial Bmp signaling switches the differentiation of crown epithelia to the root lineage in a beta-catenin-dependent manner" Mol Cell Biol (2013) 10.1128/mcb.00456-13
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Published
Oct 14, 2014
Vol/Issue
32(11)
Pages
2939-2948
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Cite This Article
Guan Yang, Jian Zhou, Yan Teng, et al. (2014). Mesenchymal TGF-βSignaling Orchestrates Dental Epithelial Stem Cell Homeostasis Through Wnt Signaling. Stem Cells, 32(11), 2939-2948. https://doi.org/10.1002/stem.1772