title: FGF signaling is necessary for the specification of the odontogenic mesenchyme.
abstract: Tooth development is initiated by signals from the oral ectoderm which induce gene expression required for tooth development in the underlying mesenchyme. In this study, we have used Su5402, an inhibitor of FGF receptor signaling, to analyze the requirement of FGF signaling during early tooth development. We show that FGF signaling is necessary for expression of Pax9, a transcription factor required for development of all teeth, in prospective incisor and molar mesenchyme until E11.0. Expression of the LIM homeobox gene Lhx7 also requires FGF signaling until E11.0 whereas expression of its homologue Lhx6 and the homeobox transcription factor Barx1 already becomes independent of FGF signaling at E10.75. In contrast, ectodermal expression of several genes thought to be important for tooth development was unaffected by the block of FGF signaling. Finally, we show that expression of the TGFbeta antagonist Dan in prospective tooth mesenchyme requires ectodermal signals and can be induced by FGF-soaked beads but is maintained in mandibular explants in the absence of FGF signaling. Together, these results demonstrate that FGF signaling is required for development of both molar and incisor teeth and suggest that specification of tooth mesenchyme involves at least two FGF-dependent steps.
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Mandler
authors.forename: A
authors.initials: A
authors.lastname: Neubüser
mesh_terms: D000818:Animals; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D046508:Culture Techniques; D016207:Cytokines; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004475:Ectoderm / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D007180:Incisor / Q000196:embryology; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008963:Molar / Q000196:embryology; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009805:Odontogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051764:PAX9 Transcription Factor; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000097577:Homeobox Protein PITX2
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018797:Cell Cycle Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051764:PAX9 Transcription Factor; D011506:Proteins; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C095587:Barx1 protein, mouse; C525810:Bmp4 protein, mouse; C496457:Fgf8 protein, mouse; C490088:Grem2 protein, mouse; C498504:LHX6 protein, mouse; C112960:LIM homeobox protein 8; C490089:Nbl1 protein, mouse; C105686:SU 5402