title: Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis.
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.
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Prochazka
authors.affiliation: 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.
authors.forename: Michaela
authors.initials: M
authors.lastname: Prochazkova
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Du
authors.affiliation: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague 4 14220, Czech Republic.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Spoutil
authors.affiliation: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague 4 14220, Czech Republic.
authors.forename: Jolana
authors.initials: J
authors.lastname: Tureckova
authors.affiliation: Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, 1500 4th Street, San Francisco, CA 94143, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Hoch
authors.affiliation: Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, 2-1 Hirosawa Wako, Saitama 351-0198, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shimogori
authors.affiliation: Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague 4 14220, Czech Republic.
authors.forename: Radislav
authors.initials: R
authors.lastname: Sedlacek
authors.affiliation: Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, 1500 4th Street, San Francisco, CA 94143, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Rubenstein
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Wittmann
authors.affiliation: 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.
authors.forename: Ophir D
authors.initials: OD
authors.lastname: Klein
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008963:Molar / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D009805:Odontogenesis / Q000502:physiology; D014070:Tooth / Q000166:cytology* / Q000196:embryology
chemical_list: D005346:Fibroblast Growth Factors