Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis

The proper positioning of organs during development is essential, yet little is known about the regulation of this process in mammals. Using murine tooth development as a model, we have found that cell migration plays a central role in positioning of the organ primordium. By combining lineage tracing, genetic cell ablation, and confocal live imaging, we identified a migratory population of Fgf8-expressing epithelial cells in the embryonic mandible. These Fgf8-expressing progenitors furnish the epithelial cells required for tooth development, and the progenitor population migrates toward a Shh-expressing region in the mandible, where the tooth placode will initiate. Inhibition of Fgf and Shh signaling disrupted the oriented migration of cells, leading to a failure of tooth development. These results demonstrate the importance of intraepithelial cell migration in proper positioning of an initiating organ. [Display omitted] •Migratory Fgf8-expressing cells are the founding population during tooth development•Intraepithelial migration is essential for proper positioning of the molar primordium•Shh serves as a guidance signal for migratory cells in the developing tooth Prochazka et al. investigate mechanisms of organ positioning using the tooth as a model. Combining lineage tracing, genetic cell ablation, and confocal live imaging, they identified a Fgf8-expressing epithelial cell population whose migration toward a Shh-expressing region in the mandible, the tooth placode initiation site, is required for tooth development.