Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth.
Epithelial-mesenchymal interactions govern the development of epidermal organs such as teeth. During the early stages of tooth development, a local ectodermal thickening which expresses several signaling molecules appears. It is believed that these in turn signal to the underlying mesenchyme triggering mesenchymal condensation and tooth development. For example, epithelially expressed Bmp4 induces Msx1 and Lef1 as well as itself in the underlying mesenchyme. In this paper we have investigated the role of four epithelial signaling molecules, Bmp2, Shh, Wnt10a, and Wnt10b, in the early inductive cascades that govern tooth development. We show that all four genes are specifically expressed in the epithelium between E11.0 and E12.0 when tooth morphogenesis is first apparent. Although Shh, Bmp2, and Wnt10b have similar, if not identical, expression patterns, each signal has a distinct molecular action on the jaw mesenchyme. Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets, Ptc and Gli for Shh and Lef1 for Wnt10b, only Bmp2 is able to induce tooth-specific expression of Msx1. Thus, there are distinct targets for all three pathways. Interestingly, both Bmp and Wnt signaling activate Lef1, making it a candidate for integrating the two distinct signaling pathways.
The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
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D016475:3T3 Cells; D029845:Amphibian Proteins; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004627:Embryonic Induction / Q000235:genetics / Q000502:physiology; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D051821:Lymphoid Enhancer-Binding Factor 1; D051957:MSX1 Transcription Factor; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009805:Odontogenesis / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014070:Tooth / Q000196:embryology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins
D029845:Amphibian Proteins; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051957:MSX1 Transcription Factor; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse