Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation.
Vertebrate organogenesis is initiated at sites that are often morphologically indistinguishable from the surrounding region. Here we have identified Pax9 as a marker for prospective tooth mesenchyme prior to the first morphological manifestation of odontogenesis. We provide evidence that the sites of Pax9 expression in the mandibular arch are positioned by the combined activity of two signals, one (FGF8) that induces Pax9 expression and the other (BMP2 and BMP4) that prevents this induction. Thus it appears that the position of the teeth is determined by a combination of two different types of signaling molecules produced in wide but overlapping domains rather than by a single localized inducer. We suggest that a similar mechanism may be used for specifying the sites of development of other organs.
Neubüser
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Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California, San Francisco 94143-0452, USA.
Peters
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Balling
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R
Martin
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GR
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004475:Ectoderm / Q000737:chemistry / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008334:Mandible / Q000737:chemistry / Q000196:embryology; D008648:Mesoderm / Q000737:chemistry / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D051764:PAX9 Transcription Factor; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology*; D014070:Tooth / Q000737:chemistry / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; D006133:Growth Substances; D009363:Neoplasm Proteins; D051764:PAX9 Transcription Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors