title: YAP overexpression affects tooth morphogenesis and enamel knot patterning.
abstract: Teeth develop through distinct morphological stages. At the cap stage, a compactly clustered and concentrically arranged cell mass, the enamel knot, appears at the tip of the enamel organ. Cells in this knot express sets of key molecules, and as such have been proposed to act as a signaling center directing tooth morphogenesis and tooth cusp formation. YAP is a transcriptional co-activator of the Hippo signaling pathway that is essential for the proper regulation of organ growth. In this study, we analyzed the tooth phenotype in transgenic mice that overexpressed a constitutively active form of YAP in the dental epithelium. We found that overexpression of YAP resulted in deformed tooth morphogenesis with widened dental lamina. In addition, the enamel knot was mislocated to the upper portion of the enamel organ, where it remained devoid of proliferating cells and contained apoptotic cells with intense Edar transcripts and reduced E-cadherin expression. Interestingly, some signaling molecules, such as Shh, Fgf4, and Wnt10a, were not expressed in this mislocated enamel knot, but remained at the tip of the enamel organ. Analysis of these data suggests that the signaling center is induced by reciprocal epithelial-mesenchymal interactions, and its induction may be independent of the enamel knot.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.forename: X P
authors.initials: XP
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000566:Amelogenesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000032:analysis; D002448:Cell Adhesion / Q000235:genetics; D018797:Cell Cycle Proteins; D053339:Edar Receptor / Q000032:analysis / Q000235:genetics; D004658:Enamel Organ / Q000002:abnormalities / Q000196:embryology*; D004847:Epithelial Cells / Q000473:pathology; D004848:Epithelium / Q000196:embryology; D051519:Fibroblast Growth Factor 4 / Q000032:analysis; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053823:Hedgehog Proteins / Q000032:analysis; D000090683:Hippo Signaling Pathway; D008648:Mesoderm / Q000196:embryology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis; D009805:Odontogenesis / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014071:Tooth Abnormalities / Q000235:genetics; D019228:Tooth Crown / Q000002:abnormalities / Q000196:embryology; D014083:Tooth Germ / Q000002:abnormalities / Q000196:embryology; D051153:Wnt Proteins / Q000032:analysis; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D018797:Cell Cycle Proteins; D053339:Edar Receptor; C506009:Edar protein, mouse; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C465570:Shh protein, mouse; D051153:Wnt Proteins; C484143:Wnt10a protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: Hippo signaling; dental lamina; epithelial-mesenchymal interaction; morphogenesis; signaling center; tooth development