title: Convergent signalling through Fgfr2 regulates divergent craniofacial morphogenesis.
abstract: Fibroblast growth factor receptor 2 (Fgfr2) has two splice variants IIIb and IIIc, which are unique in function and localization. Signalling through Fgfr2IIIb controls epithelial-mesenchymal interactions, which regulate morphogenesis during the development of several organs including the palate and tooth. In this study, we confirm that molar tooth development in Fgfr2IIIb(-/-) mice is arrested early in development and that the molar teeth of Fgf10(-/-) mice develop through all the normal stages of morphogenesis. We show that the molar phenotype of Fgfr2IIIb(-/-) mice is, in part, owing to reduced cell proliferation in both epithelial and mesenchymal compartments. We also show that the developing molar teeth of Fgf10(-/-) mice exhibit reduced cell proliferation. However, this reduction is not sufficient to arrest molar development. Recent evidence has indicated that Fgfr2IIIb/Fgf10 signalling is active in the calvaria in some pathological situations as heterozygous deletion of Fgfr2 exon IIIc in mice leads to ectopic expression of Fgfr2IIIb in the calvarial bones and causes craniosynostosis. Here, we investigate the mRNA expression of Fgfr2IIIb and Fgfr2IIIc as well as their ligands Fgf3, -7 and -10 in the developing murine tooth, palate and calvaria. We show that Fgf7 is expressed in the calvarial mesenchyme adjacent to the developing frontal bone and Fgf10 is expressed by osteoprogenitors in the developing frontal bone condensation. Taken together, we highlight the overlapping roles of Fgfr2IIIb/Fgf10 signalling in controlling epithelial-mesenchymal interactions during normal palate and tooth morphogenesis and how elevated signalling through Fgfr2IIIb/Fgf10 solely within the mesenchyme can result in abnormal calvarial morphogenesis.
authors.affiliation: Department of Orthodontics, Institute of Dentistry, University of Helsinki, Helsinki, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Veistinen
authors.forename: Thomas
authors.initials: T
authors.lastname: Aberg
authors.forename: David P C
authors.initials: DP
authors.lastname: Rice
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005145:Face; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000502:physiology*; D015398:Signal Transduction; D012886:Skull / Q000254:growth & development*; D014070:Tooth / Q000254:growth & development*
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D051497:Receptor, Fibroblast Growth Factor, Type 2