Sox2 marks epithelial competence to generate teeth in mammals and reptiles

Development (Impact Factor: 6.46). 03/2013; 140(7). DOI: 10.1242/dev.089599
Source: PubMed


Tooth renewal is initiated from epithelium associated with existing teeth. The development of new teeth requires dental epithelial cells that have competence for tooth formation, but specific marker genes for these cells have not been identified. Here, we analyzed expression patterns of the transcription factor Sox2 in two different modes of successional tooth formation: tooth replacement and serial addition of primary teeth. We observed specific Sox2 expression in the dental lamina that gives rise to successional teeth in mammals with one round of tooth replacement as well as in reptiles with continuous tooth replacement. Sox2 was also expressed in the dental lamina during serial addition of mammalian molars, and genetic lineage tracing indicated that Sox2+ cells of the first molar give rise to the epithelial cell lineages of the second and third molars. Moreover, conditional deletion of Sox2 resulted in hyperplastic epithelium in the forming posterior molars. Our results indicate that the Sox2+ dental epithelium has competence for successional tooth formation and that Sox2 regulates the progenitor state of dental epithelial cells. The findings imply that the function of Sox2 has been conserved during evolution and that tooth replacement and serial addition of primary teeth represent variations of the same developmental process. The expression patterns of Sox2 support the hypothesis that dormant capacity for continuous tooth renewal exists in mammals.

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    • "Tracking of Sox2 + cells has shown that they contribute to the epithelium of the developing second and third molars in the mouse (Juuri et al., 2013b). The key role of Sox2 in tooth development has been shown by conditionally deleting Sox2, resulting in aberrant formation of the dental epithelium (Juuri et al., 2013b). A second Sox transcription factor expressed during dental development is Sox9. "
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    ABSTRACT: During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells.
    Biology Open 11/2015; DOI:10.1242/bio.013672 · 2.42 Impact Factor
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    • "For instance, the lineage tracing of the Gli1+ cell population demonstrated the involvement of these cells in the long-term renewal of the incisor epithelial compartments (Seidel et al., 2010). More recently, two other cell populations localized in the labial CL were shown to participate in incisor renewal via genetic fate mapping, namely Sox2+ and Bmi1+ cells (Juuri et al., 2012; Biehs et al., 2013). Interestingly, the Sox2+ cells, Bmi1+ cells and Gli1+ cell populations (Figure 4) might not completely overlap and seem to have different dynamics during tooth homeostasis, reflecting a possible hierarchy of stem cells in the hypselodont tooth renewing. "
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    ABSTRACT: A major challenge for current evolutionary and developmental biology research is to understand the evolution of morphogenesis and the mechanisms involved. Teeth are well suited for the investigation of developmental processes. In addition, since teeth are composed of hard-mineralized tissues, primarily apatite, that are readily preserved, the evolution of mammals is well documented through their teeth in the fossil record. Hypsodonty, high crowned teeth with shallow roots, and hypselodonty, ever-growing teeth, are convergent innovations that have appeared multiple times since the mammalian radiation 65 million years ago, in all tooth categories (incisors, canines, premolars, and molars). A shift to hypsodonty, or hypselodonty, during mammalian evolution is often, but not necessarily, associated with increasingly abrasive diet during important environmental change events. Although the evolution of hypsodonty and hypselodonty is considered to be the result of heterochrony of development, little has been known about the exact developmental mechanisms at the origin of these morphological traits. Developmental biologists have been intrigued by the mechanism of hypselodonty since it requires the maintenance of continuous crown formation during development via stem cell niche activity. Understanding this mechanism may allow bioengineered tooth formation in humans. Hypsodonty and hypselodonty are thus examples of phenotypic features of teeth that have both impacts in understanding the evolution of mammals and holds promise for human tooth bioengineering.
    Frontiers in Physiology 08/2014; 5:324. DOI:10.3389/fphys.2014.00324 · 3.53 Impact Factor
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    • "DE-SCs are characterized by their signature molecules. Sox2 has been identified as a stem cell marker to maintain their lineages [5], [6]. DE-SCs give rise to all the dental epithelia including the inner and outer enamel epithelia (IEE, also called the inner dental epithelium [IDE], and OEE, respectively), the stellate reticulum (SR), the stratum intermedium (SI), and ameloblasts. "
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    ABSTRACT: Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.
    PLoS ONE 06/2014; 9(6):e99991. DOI:10.1371/journal.pone.0099991 · 3.23 Impact Factor
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