Journal
DEVELOPMENTAL CELL
Volume 35, Issue 6, Pages 713-724Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2015.11.025
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Funding
- NIH [R01-DE021420, R01-DE024988, F32-MH081431, R01-NS34661, S10-RR026758]
- Weston Havens Foundation
- Academy of Sciences of the Czech Republic [RVO 68378050]
- BIOCEV-Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University [CZ.1.05/1.1.00/02.0109]
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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.
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