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Tooth Specification & Crown Development: Part 2 Name: Laura LimLearning Objectives •Describe the role of specific odontogenic homeobox genes in dictating the formation of incisiform, caniniform and molariformfor teeth •Rcommunication and the enamel knot in determining crown shapel formation •Einformation to tooth crown morphogenesisms that link patterning •Recognise how defects in the respective pathways link to failure in normal tooth morphogenesisAnterior-Posterior Patterning of Dental Arch • FGF-8 and BMP-4 contribute to formation and differentiation of teeth along the axis • Ensures teeth are organized in a specific order with distinct characteristics along the length of the jaw • Via positional signalling, initiation of tooth development, interaction with other signalling pathways • Dysregulation can lead to abnormalities in tooth patterning and developmentBuccal-Lingual Control in Dental Arch • demonstrates a gradient of expression within odontogenic mesenchyme that predominates lingually • Suppression of BMP4-Msx1 pathway • If lacking function of Osr2, will lead to development of supernumerary tooth on lingual side Bmp4–Msx1 is upregulated in lingual regions of the developing jaw—an activity that is sufficient to induce supernumerary tooth formation in this regionEpithelial-Mesenchymal Interaction ooth Crown?Initiation of T ooth Development • Sonic Hedgehog Activity • epithelium causing ectodermal thickeningtooth germ • Leads to invagination of epithelium into ectomesenchyme -> formation of the tooth bud • Inhibition of Shh -> arrested tooth development, reduced ectodermal proliferation, reduction in tooth size • Shh and Wnt-7b • WNt-7b is expressed continuously through ectoderm except tooth forming regions that expresses Shh gene • Overexpression of Wnt-7b downregulates Shh gene, leads to arrest of tooth development at ectodermal thickening stageT ooth Morphogenesis • process whereby the dental lamina generates a tooth with a characteristic morphology • transition from bud to cap stage is a critical step in tooth morphogenesis, marking the onset of development of the tooth crown • helps to establish fundamental coronal architecture prior to more detailed sculpting of cuspal morphology, cellular differentiation and finally, mineralization • enamel knot- a discreet non-proliferating and transient signalling centre intimately involved with the regulation of tooth shapeEnamel Knot • including members of the bone morphogenetic protein (BMP), fibroblast growth factor (FGF), WNT and Hedgehog families • signalling from underlying ectomesenchyme during bud stage • Bmp4 signalling from the early epithelium establishing Bmp4 expression in the underlying mesenchyme, which occurs via the induction of Msx • via p21 induction within the epithelium and ultimately, in the rapid death of this structure via Bmp4-induced apoptosis within these same cellsWnt Signalling • important determinants of normal tooth developmentare • Lef1 essential for tooth bud progression beyond bud stage • B-catenin also a determinant of tooth number • Increased Wnt signalling through B-catenin produce increase in tooth number • Modulation of WNT and BMP signalling in controlling tooth number • Ectodin (BMP inhibitor) binds and inhibits to Lrp4 to prevent • Ectodin present in mesenchyme and epithelium but not enamel knot•Shh is required for assymetric development of dental cap (lingual aspect) •Enamel knot cells are eventually removed by apoptosis (day E14/15) •Signaling molecules produced in the primary enamel knot will subsequently induce formation of secondary enamel knots at sites of cusps in molar teeth in a context dependent manner (expression of homeobox genes in the underlying ectomesenchyme) • FGF-4 signaling may dictate the spacing of enamel knotsEctodysplasin-Edar Signaling •Responsible for regulation of dental placode size •Edar expression only expressed within the enamel knot •Over-activation of this signalling pathway can lead to larger dental placodes and extra teeth •Defects in the signalling pathway can lead to defects in the cusps of molar teeth / X-linked hypohidrotic ectodermal dysplasia Which is essential in the buccal lingual control in tooth development? A. Msx-1 B. Pax-9 C. Osr-2 D. BMP-4 Which is essential in the buccal lingual control in tooth development? A. Msx-1 B. Pax-9 C. Osr-2 D. BMP-4 Which signaling pathway is essential in ectodermal thickening during tooth development? A. Ectodysplasin-Edar signaling pathway B. Wnt signaling C. Shh signaling D. BMP signaling Which signaling pathway is essential in ectodermal thickening during tooth development? A. Ectodysplasin-Edar signaling pathway B. Wnt signaling C. Shh signaling D. BMP signalingThank you!