Epithelial topography for repetitive tooth formation

Gaete, Marcia; Fons, Juan M.; Popa, Elena; Chatzeli, Lemonia; Tucker, Abigail S.

doi:10.1242/bio.013672

Cited by 19 publications

(32 citation statements)

References 35 publications

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“…The interdental lamina does not produce teeth, in contrast to the tooth-producing successional dental lamina located adjacent to the first generation teeth. Sox2 and Sox9 have recently been shown to have complementary patterns of expression in the growing molar tail, which will form the serially added molars at the back of the mouth (Gaete et al, 2015). We therefore analysed the expression of these two progenitor markers in the two parts of the minipig dental lamina, and compared their expression with that in the RSDL in the mouse.…”

Section: Resultsmentioning

confidence: 99%

“…The Bmp4 probe was a gift from Prof. Karen Lyons (University of California at Los Angeles, USA; Lyons et al, 1990); the ectodin probe (Wise) was a gift from Dr Atsushi Ohazama (King's College London, UK;Ohazama et al, 2008); Fgf3 and Fgf4 probes were gifts from Prof. Ivor Mason (King's College London, UK; Mahmood et al, 1996); the Pax9 probe was a gift from Dr Heiko Peters (Newcastle University, UK; Peters et al, 1998); and the Shh probe was a gift from Prof. Andy McMahon (University of Southern California, Los Angeles, USA; Bitgood and McMahon, 1995). In situ hybridisation of craniofacial sections was carried out as previously described by Gaete et al (2015).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Revitalising the rudimentary replacement dentition in the mouse

2019

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Most mammals have two sets of teeth (diphyodont)a deciduous dentition replaced by a permanent dentition; however, the mouse possesses only one tooth generation (monophyodont). In diphyodonts, the replacement tooth forms on the lingual side of the first tooth from the successional dental lamina. This lamina expresses the stem/progenitor marker Sox2 and has activated Wnt/β-catenin signalling at its tip. Although the mouse does not replace its teeth, a transient rudimentary successional dental lamina (RSDL) still forms during development. The mouse RSDL houses Sox2-positive cells, but no Wnt/β-catenin signalling. Here, we show that stabilising Wnt/ β-catenin signalling in the RSDL in the mouse leads to proliferation of the RSDL and formation of lingually positioned teeth. Although Sox2 has been shown to repress Wnt activity, overexpression of Wnts leads to a downregulation of Sox2, suggesting a negative-feedback loop in the tooth. In the mouse, the first tooth represses the formation of the replacement, and isolation of the RSDL is sufficient to induce formation of a new tooth germ. Our data highlight key mechanisms that may have influenced the evolution of replacement teeth. This article has an associated 'The people behind the papers' interview.

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Section: Resultsmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Revitalising the rudimentary replacement dentition in the mouse

2019

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“…We therefore used ex vivo organ cultures to examine the effect of increased Wnt/ β-catenin signaling on the formation of M2 in control mice. M2 develops from the posterior extension of the M1 epithelium, also referred to as posterior dental lamina, posterior tail (tip) and continual lamina (Juuri et al, 2013;Gaete et al, 2015;Juuri and Balic, 2017). We dissected mouse embryonic M1 tooth germs at the stage when M2 is initiated (E14.5) and the continual lamina, which indicates the starting point of M2 development, is clearly visible (Fig.…”

Section: Stimulation Of Wnt/β-catenin Signaling In Embryonic Molars Bmentioning

confidence: 99%

Mesenchymal Wnt/β-catenin signaling limits tooth number

et al. 2018

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Tooth agenesis is one of the predominant developmental anomalies in humans, usually affecting the permanent dentition generated by sequential tooth formation and, in most cases, caused by mutations perturbing epithelial Wnt/β-catenin signaling. In addition, loss-of-function mutations in the Wnt feedback inhibitor lead to human tooth agenesis. We have investigated the functions of Wnt/β-catenin signaling during sequential formation of molar teeth using mouse models. Continuous initiation of new teeth, which is observed after genetic activation of Wnt/β-catenin signaling in the oral epithelium, was accompanied by enhanced expression of Wnt antagonists and a downregulation of Wnt/β-catenin signaling in the dental mesenchyme. Genetic and pharmacological activation of mesenchymal Wnt/β-catenin signaling negatively regulated sequential tooth formation, an effect partly mediated by Bmp4., a gene whose loss-of-function mutations result in sequential formation of supernumerary teeth in the human cleidocranial dysplasia syndrome, suppressed the expression of Wnt inhibitors and in dental mesenchyme. Our data indicate that increased mesenchymal Wnt signaling inhibits the sequential formation of teeth, and suggest that / antagonistic interactions modulate the level of mesenchymal Wnt/β-catenin signaling, underlying the contrasting dental phenotypes caused by human and mutations.

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“…Additionally, SOX2 expression, which is a marker of DESCs in M1 [3] , is associated with sequential development directed to the posterior position [1] . Marcia Gaete et al reported that epithelium of the anterior-molar tail could grow by the posterior movement of epithelial cells, followed by infolding and stratification involving a population of SOX2 + /SOX9 + cells [4] .…”

Section: Introductionmentioning

confidence: 99%

LGR4 is required for sequential molar development

Yamakami

Kohashi

Oyama

et al. 2016

Biochemistry and Biophysics Reports

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Tooth development requires proliferation, differentiation, and specific migration of dental epithelial cells, through well-organized signaling interactions with mesenchymal cells. Recently, it has been reported that leucine-rich repeat-containing G protein coupled receptor 4 (LGR4), the receptor of R-spondins, is expressed in many epithelial cells in various organs and tissues and is essential for organ development and stem cell maintenance. Here, we report that LGR4 contributes to the sequential development of molars in mice. LGR4 expression in dental epithelium was detected in SOX2+ cells in the posterior end of the second molar (M2) and the early tooth germ of the third molar (M3). In keratinocyte-specific Lgr4-deficient mice (Lgr4K5 KO), the developmental defect became obvious by postnatal day 14 (P14) in M3. Lgr4K5 KO adult mice showed complete absence or the dwarfed form of M3. In M3 development in Lgr4K5 KO mice, at Wnt/β-catenin signal activity was down-regulated in the dental epithelium at P3, as indicated by lymphoid enhancer-binding factor-1 (LEF1) expression. We also confirmed the decrease, in dental epithelium of Lgr4K5 KO mice, of the number of SOX2+ cells and the arrest of cell proliferation at P7, and observed abnormal differentiation at P14. Our data demonstrated that LGR4 controls the sequential development of molars by maintaining SOX2+ cells in the dental epithelium, which have the ability to form normal molars.

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Epithelial topography for repetitive tooth formation

Cited by 19 publications

References 35 publications

Revitalising the rudimentary replacement dentition in the mouse

Revitalising the rudimentary replacement dentition in the mouse

Mesenchymal Wnt/β-catenin signaling limits tooth number

LGR4 is required for sequential molar development

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