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Dev Cell. 2015 Dec 21;35(6):713-24. doi: 10.1016/j.devcel.2015.11.025.

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

Author information

1
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA; Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague 4 14220, Czech Republic.
2
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
3
Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague 4 14220, Czech Republic.
4
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, 1500 4th Street, San Francisco, CA 94143, USA.
5
Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, 2-1 Hirosawa Wako, Saitama 351-0198, Japan.
6
Department of Cell and Tissue Biology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
7
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA; Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: ophir.klein@ucsf.edu.

Abstract

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.

PMID:
26702830
PMCID:
PMC4710359
DOI:
10.1016/j.devcel.2015.11.025
[Indexed for MEDLINE]
Free PMC Article

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