Abstract
ABSTRACTDuring 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.
Highlights
Teeth are important organs required for eating and speaking, and tooth loss is a common problem for society
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
The dissected molar region gives rise to three molars in culture that appear sequentially from its posterior end In order to visualise morphological changes and the timing of appearance of successional molars in culture, we dissected out the first molar placode and its posterior tail (Fig. 1A, M1 and arrowhead) and performed organotypic culture over 7 days
Summary
Teeth are important organs required for eating and speaking, and tooth loss is a common problem for society. The biological replacement of missing teeth is the ultimate goal for clinicians, either by implanting a bioengineered tooth or by stimulating dental tissue to form a new organ To accomplish this goal it is necessary to understand the mechanisms involved during tooth initiation. Teeth can be formed de-novo, i.e. initiate for the first time from new placodes, or can be formed in succession, i.e. initiate from preexisting dental tissue This last method, known as successional tooth development, can be observed during the formation of molar teeth. When the molar placode is dissected out and cultured in vitro at E12 the complete molar dentition forms in sequence maintaining the normal crown shapes and proportions (Lumsden, 1979) At this early stage of dental development, all the patterning information to create successional teeth is already present in the molar placode. Culturing the molar placode is a common tool in dental research and has been used to understand the control of the tooth number and cusp pattern (Jernvall and Thesleff, 2012; Kavanagh et al, 2007)
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