An understanding of the factors that promote or inhibit tooth development is essential for designing biological tooth replacements. The embryonic mouse dentition provides an ideal system for studying such factors because it consists of two types of tooth primordia. One type of primordium will go on to form a functional tooth, whereas the other initiates development but arrests at or before the bud stage. This developmental arrest contributes to the formation of the toothless mouse diastema. It is accompanied by the apoptosis of the rudimentary diastemal buds, which presumably results from the insufficient activity of anti-apoptotic signals such as fibroblast growth factors (FGFs). We have previously shown that the arrest of a rudimentary tooth bud can be rescued by inactivating Spry2, an antagonist of FGF signaling. Here, we studied the role of the epithelial cell death and proliferation in this process by comparing the development of a rudimentary diastemal tooth bud (R(2)) and the first molar in the mandibles of Spry2(-/-) and wild-type (WT) embryos using histological sections, image analysis and 3D reconstructions. In the WT R(2) at embryonic day 13.5, significantly increased apoptosis and decreased proliferation were found compared with the first molar. In contrast, increased levels of FGF signaling in Spry2(-/-) embryos led to significantly decreased apoptosis and increased proliferation in the R(2) bud. Consequently, the R(2) was involved in the formation of a supernumerary tooth primordium. Studies of the revitalization of rudimentary tooth primordia in mutant mice can help to lay the foundation for tooth regeneration by enhancing our knowledge of mechanisms that regulate tooth formation.

Department of Teratology Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic

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Role of Cell Death in Cellular Processes During Odontogenesis

Developmental variability channels mouse molar evolution

Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning

Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation

Three-dimensional analysis of the early development of the dentition

Apoptotic signaling in mouse odontogenesis

Patterning by heritage in mouse molar row development