Three-dimensional analysis of molar development in the mouse from the cap to bell stage

During four days of prenatal development in the mouse, the morphology of the first lower molar moves from the early cap to the bell stage. Five phenomena characterize this period: growth of the tooth germ; development of the cervical loop; histogenesis of the enamel organ; folding of the epithelial-mesenchymal junction associated with cusp formation; and change in cellular heterogeneity in the mesenchyme. All these processes are controlled by epithelial-mesenchymal interactions. These complex histo-morphogenetic events have been documented using histological sections and 3D reconstructions. When combined with functional tests in vitro, this approach allowed searching for possible relationships between simultaneous changes occurring in both the epithelial and ecto-mesenchymal compartments. Parallel changes that occur in the two tissues could result from different mechanisms, as illustrated by the increasing number of pre-odontoblasts and pre-ameloblasts during crown growth. Cell division was involved mainly in the ecto-mesenchyme, while proliferation and cell re-organization occurred in the inner dental epithelium. 3D reconstructions also raised still unsolved questions, such as the possible relationship between cusp size and spatial specification of cell kinetic parameters, changes in cell position within the inner dental epithelium, and tracing cell migration in the mesenchyme during development.