title: Identification of a novel putative signaling center, the tertiary enamel knot in the postnatal mouse molar tooth.
abstract: The final shape of the molar tooth crown is thought to be regulated by the transient epithelial signaling centers in the cusp tips, the secondary enamel knots (SEKs), which are believed to disappear after initiation of the cusp growth. We investigated the developmental fate of the signaling center using the recently characterized Slit1 enamel knot marker as a lineage tracer during morphogenesis of the first molar and crown calcification in the mouse. In situ hybridization analysis showed that after Fgf4 downregulation in the SEK, Slit1 expression persisted in the deep compartment of the knot. After the histological disappearance of the SEK, Slit1 expression was evident in a novel epithelial cell cluster, which we call the tertiary enamel knot (TEK) next to the enamel-free area (EFA)-epithelium at the cusp tips. In embryonic tooth, Slit1 was also observed in the stratum intermedium (SI) and stellate reticulum cells between the parallel SEKs correlating to the area where the inner enamel epithelium cells do not proliferate. After birth, the expression of Slit1 persisted in the SI cells of the transverse connecting lophs of the parallel cusps above the EFA-cells. These results demonstrate the presence of a novel putative signaling center, the TEK, in the calcifying tooth. Moreover, our results suggest that Slit1 signaling may be involved in the regulation of molar tooth shape by regulating epithelial cell proliferation and formation of EFA of the crown.
authors.affiliation: Department of Anatomy and Cell Biology, University of Bergen, Arstadveien 19, N-5009, Bergen, Norway. keijo.luukko@pki.uib.no
authors.forename: Keijo
authors.initials: K
authors.lastname: Luukko
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Løes
authors.forename: Tomasz
authors.initials: T
authors.lastname: Furmanek
authors.forename: Karianne
authors.initials: K
authors.lastname: Fjeld
authors.forename: Inger Hals
authors.initials: IH
authors.lastname: Kvinnsland
authors.forename: Paivi
authors.initials: P
authors.lastname: Kettunen
mesh_terms: D029845:Amphibian Proteins; D000818:Animals; D000831:Animals, Newborn; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D003743:Dental Enamel / Q000254:growth & development* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D021621:Imaging, Three-Dimensional; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008963:Molar / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009805:Odontogenesis / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D014083:Tooth Germ / Q000196:embryology; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
chemical_list: D029845:Amphibian Proteins; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; C492289:SLIT1 protein, human; C120010:Slit1 protein, mouse; D014157:Transcription Factors; C085389:WNT5A protein, human; C490674:WNT6 protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C095936:Wnt6 protein, mouse; D005346:Fibroblast Growth Factors