title: Inhibition of apoptosis in the primary enamel knot does not affect specific tooth crown morphogenesis in the mouse.
abstract: The enamel knot (EK), located in the center of cap-stage tooth germs, is a transitory cluster of non-dividing epithelial cells, eventually linked to the outer dental epithelium by the enamel septum (ES). It might act as a signaling center providing positional information for tooth morphogenesis and could regulate the growth of tooth cusps through the induction of secondary signaling EKs. The EK undergoes apoptosis, which could constitute a mechanism whereby the signaling functions of this structure are terminated. Recently, we demonstrated the segregation of 5-bromo-2'-deoxyuridine (BrdU) negative inner dental epithelial (IDE) cells of the EK into as many individual groups of cells as cusps will form and suggested a morphogenetic role for these particular IDE cells. Using Z-VAD-fmk, a specific caspase inhibitor, apoptosis in the primary EK of first mouse lower cap-staged molars and lower incisors cultured in vitro was abrogated. No obvious histological alterations were observed in the incisors, whereas a prominent EK and an ES connecting the outer dental epithelium (ODE) and the BrdU negative IDE cells capping cusp L2 were observed in the molars. EK specific transcription (Shh, Msx-2, Bmp-2, Bmp-4) was down-regulated in the body of these structures with the exception of the associated IDE cells. In these experimental conditions, segregation of non-dividing transcriptionally active IDE cells occurred and a normal cusp pattern was expressed.
authors.affiliation: INSERM U-424, U.F.R d'Odontologie de Strasbourg, France.
authors.forename: R
authors.initials: R
authors.lastname: Coin
authors.forename: S
authors.initials: S
authors.lastname: Kieffer
authors.forename: H
authors.initials: H
authors.lastname: Lesot
authors.forename: J L
authors.initials: JL
authors.lastname: Vonesch
authors.forename: J V
authors.initials: JV
authors.lastname: Ruch
mesh_terms: D000818:Animals; D017209:Apoptosis; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D003743:Dental Enamel / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D009805:Odontogenesis / Q000235:genetics; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D015534:Trans-Activators; D016212:Transforming Growth Factor beta
chemical_list: 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; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D011506:Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D001973:Bromodeoxyuridine