Identification of inner and outer cell proliferation centers during fetal tooth morphogenesis

Patterns of cell division have been examined in the proliferative cervical loop tissues of fetal rabbit incisor tooth organs. Evaluation of the distribution patterns of silver grains, resulting from the incorporation of [3H]-thymidine into newly synthesized DNA within tooth organs in vitro, resulted in identification of two proliferation centers: (1) an inner center consisting of inner enamel epithelial cells (i.e., preameloblasts) and predontoblasts ; and (2) an outer center consisting of outer enamel epithelium and adjacent mesenchyme. In contrast to the classically held description of epithelial cell differentiation during tooth morphogenesis, our data suggest that outer enamel epithelial cells do not migrate around the cervical loop and do not provide progenitor cells for subsequent ameloblast cytodifferentiation. During tooth development, epithelial and mesenchymal cells, which arise from either an inner or outer proliferative center, migrate in distal directions relative to the proliferative sites. Therefore, the progenitor cells for ameloblasts and odontoblasts were found to be localized in the inner proliferation zone. The implications of these findings regarding the development of continuously erupting rabbit and rodent incisor tooth organs are discussed in the context of a model.