Pathways and Fate of Migratory Cells During Late Tooth Organogenesis

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Abstract
Tissue recombination experiments and cell lineage analyses of the developing neural crest have documented the role and central pathways of migratory cells during early craniofacial development. In the present study, regional pathways of cells during late peripheral morphogenesis were investigated using the crown stage tooth organ as a model. Homing targets during tooth integument formation were analyzed to understand the fate of migratory cells involved in late tooth organogenesis and the developmental origin of periodontal tissues. After surgical removal of the oral mucosa, the oral aspect of the dental follicle of lower first mouse molar teeth was labeled using a fluorescent contact dye. Following sacrifice after 0, 2, 4, and 6 days, labeled cells were detected in the dental follicle, in the alveolar bone, and in the periodontal ligament adjacent to the molar root. The distribution of labeled tissues was reconstructed three-dimensionally via confocal microscopy. Using a tooth molar organ culture system, labeled cells within the dental follicle were documented traveling in the apical direction. Our results indicated that cell migration during tooth organogenesis was following specific pathways and that cells within the circumference of the dental follicle were migrating in the apical direction. We speculate that migratory cells passing through the dental follicle connective tissue may contribute to the formation of the periodontium. The present documentation visualizes pathways, role, and dynamics of extensive cell movements during late tooth organogenesis.