title: Expression analysis of candidate genes regulating successional tooth formation in the human embryo.
abstract: Human dental development is characterized by formation of primary teeth, which are subsequently replaced by the secondary dentition. The secondary dentition consists of incisors, canines, and premolars, which are derived from the successional dental lamina of the corresponding primary tooth germs; and molar teeth, which develop as a continuation of the dental lamina. Currently, very little is known about the molecular regulation of human successional tooth formation. Here, we have investigated expression of three candidate regulators for human successional tooth formation; the Fibroblast Growth Factor-antagonist SPROUTY2, the Hedgehog co-receptor GAS1 and the RUNT-related transcription factor RUNX2. At around 8 weeks of development, only SPROUTY2 showed strong expression in both epithelium and mesenchyme of the early bud. During the cap stage between 12-14 weeks, SPROUTY2 predominated in the dental papilla and inner enamel epithelium of the developing tooth. No specific expression was seen in the successional dental lamina. GAS1 was expressed in dental papilla and follicle, and associated with mesenchyme adjacent to the primary dental lamina during the late cap stage. In addition, GAS1 was identifiable in mesenchyme adjacent to the successional lamina, particularly in the developing primary first molar. For RUNX2, expression predominated in the dental papilla and follicle. Localized expression was seen in mesenchyme adjacent to the primary dental lamina at the late cap stage; but surprisingly, not in the early successional lamina at these stages. These findings confirm that SPROUTY2, GAS1, and RUNX2 are all expressed during early human tooth development. The domains of GAS1 and RUNX2 are consistent with a role influencing function of the primary dental lamina but only GAS1 transcripts were identifiable in the successional lamina at these early stages of development.
authors.affiliation: Department of Conservative Dentistry, Dental Institute, King's College London London, UK ; Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London London, UK.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Olley
authors.forename: Ryan
authors.initials: R
authors.lastname: Olley
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London London, UK ; Department of Orthodontics, Dental Institute, King's College London London, UK.
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Xavier
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London London, UK ; Department of Orthodontics, Dental Institute, King's College London London, UK.
authors.forename: Maisa
authors.initials: M
authors.lastname: Seppala
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London London, UK.
authors.forename: Ana A
authors.initials: AA
authors.lastname: Volponi
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London London, UK ; Department of Orthodontics, Dental Institute, King's College London London, UK.
authors.forename: Fin
authors.initials: F
authors.lastname: Geoghegan
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, Dental Institute, King's College London London, UK ; Department of Orthodontics, Dental Institute, King's College London London, UK.
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Cobourne
keywords: GAS1; RUNX2; SPROUTY2; gene expression; human tooth development; primary dental lamina; successional dental lamina; three-dimensional reconstruction