Molar tooth development in caspase-3 deficient mice.

Tooth morphogenesis is accompanied by apoptotic events which show restricted temporospatial patterns suggesting multiple roles in odontogenesis. Dental apoptosis seems to be caspase dependent and caspase-3 has been shown to be activated during dental apoptosis.Caspase-3 mutant mice on different genetic backgrounds were used to investigate alterations in dental apoptosis and molar tooth morphogenesis. Mouse embryos at E15.5 were analyzed to reveal any changes in enamel knots, which are transient structures eliminated by apoptosis. In caspase-3(-/-) mice on the B57BL/6 background, disorganization of the epithelium was found in the original primary enamel knot area and confirmed by altered expression of Shh. Despite this early defect in molar tooth development, these mutants showed correct formation of secondary enamel knots as indicated by Fgf-4 expression. Analyses of adult molar teeth did not reveal any major alterations in tooth shape, enamel structure or pattern when compared to heterozygote littermates. In caspase-3(-/-) mice on the 129X1/SvJ background, no defects in tooth development were found except the position of the upper molars which developed more posteriorly in the oral cavity. This is likely, however, to be a secondary defect caused by a physical squashing of the face by the malformed brain. The results suggest that although caspase-3 becomes activated and may be essential for dental apoptosis, it does not seem fundamental for formation of normal mineralised molar teeth.

Proliferation and apoptosis in early molar morphogenesis-- voles as models in odontogenesis.

Proliferation and apoptosis play crucial roles in the development of multicellular organisms. Their precise balance is necessary for tissue homeostasis throughout life. The developing dentition is a suitable model to study proliferation and apoptosis during embryogenesis, but the corresponding studies have been carried out principally in the mouse. The present study aimed to examine proliferation and apoptosis in the vole (Microtus sp., Rodentia) during the early morphogenesis of the first upper molar and compare it to what is known from the mouse. To this end, apoptosis and proliferation were investigated using histology and computer-aided 3D reconstruction. Mitoses accumulated predominantly in the developing cervical loop. Apoptosis during early odontogenesis showed highly specific spatio-temporal patterns in the dental epithelium. Apoptotic bodies were localised in non-dividing cell populations. They accumulated in the same places as described in the mouse: antemolar vestiges (ED 12.5 15.5), enamel knot (ED 14.5 15.5), stalk and palatally along the whole first molar tooth germ longitudinal axis (ED 15 - 15.5). Early tooth development in the field vole, including the distribution of apoptosis and mitosis, is very similar to that reported in the mouse, with the exception of the antemolar region. The microtine antemolar vestige is preserved longer than the murine one. It is conceivable that additional distinct differences in morphogenetic processes appear later in tooth development.