The distribution of BrdU- and TUNEL-positive cells during odontogenesis in mouse lower first molars

This study investigated the minute distribution of both proliferating and non-proliferating cells, and cell death in the developing mouse lower first molars using 5-bromo-2'-deoxyuridine (BrdU) incorporation and the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) double-staining technique. The distribution pattern of the TUNEL-positive cells was more notable than that of the BrdU-positive cells. TUNEL-positive cells were localized in the following six sites: (1) in the most superficial layer of the dental epithelium during the initiation stage, (2) in the dental lamina throughout the period during which tooth germs grow after bud formation, (3) in the dental epithelium in the most anterior part of the antero-posterior axis of the tooth germ after bud formation, (4) in the primary enamel knot from the late bud stage to the late cap stage, (5) in the secondary enamel knots from the late cap stage to the late bell stage, and (6) in the stellate reticulum around the tips of the prospective cusps after the early bell stage. These peculiar distributions of TUNEL-positive cells seemed to have some effect on either the determination of the exact position of the tooth germ in the mandible or on the complicated morphogenesis of the cusps. The distribution of BrdU-negative cells was closely associated with TUNEL-positive cells, which thus suggested cell arrest and the cell death to be essential for the tooth morphogenesis.