Effects of BMP-7 on mouse tooth mesenchyme and chick mandibular mesenchyme.
(25/1158)
BMP-7 is a member of the BMP family of signaling molecules that are thought to play key roles in mediating inductive events during embryogenesis. In the present study the possible roles of BMP-7 in mediating inductive events during the initiation phase of odontogenesis and mandibular morphogenesis were investigated. To do so, we have examined the effects of agarose beads soaked in recombinant BMP-7 on E11 mouse molar-forming mesenchyme and stage 23 chick mandibular mesenchyme, and analyzed the patterns of expression of Bmp-7 in developing mouse and chick first branchial arches. Beads releasing BMP-7 induced a translucent zone, cellular proliferation, and expression of Msx-1, Msx-2, and Bmp-4 in molar-forming mesenchyme after 24 hr. The effects of BMP-7 on molar-forming mesenchyme are similar to the effects of BMP-4 and are consistent with their overlapping patterns of expression in the thickened epithelium of the early developing tooth buds, which is suggestive of cooperative and/or redundant roles of BMPs in mediating the inductive interactions during the early stages of odontogenesis. Our studies in the developing chick mandible showed that Bmp-7 is expressed in the mandibular epithelium. In the absence of mandibular epithelium, BMP-7 beads maintained cell proliferation and Msx expression in the medial mandibular mesenchyme and were able to induce cell proliferation, cell death, and Msx expression in the lateral chick mandibular mesenchyme. The effects of BMP-7 on the expression of Msx genes in lateral chick mandibular mesenchyme, although different from the effects of lateral mandibular epithelium, are similar to the effects of epithelium from the medial region where multiple Bmps are expressed. We also showed that laterally placed BMP-7 beads induced ectopic expression of Msx genes and changes in the development of posterior skeletal elements in the maxillary and mandibular arches. However, despite its proliferative effects on mandibular mesenchyme, BMP-7 did not support the directional outgrowth of the mandible. These observations suggest that epithelial-mesenchymal interactions in the medial region of the mandibular arch regulating directional outgrowth of the mandibular mesenchyme are mediated by cooperative interactions between BMPs and other growth factors. Our observations also indicated that EGF, another growth factor implicated in mediating epithelial-mesenchymal interactions in the initiation phase of odontogenesis and morphogenesis of the developing mandible, induces an extensive translucent zone and cellular proliferation in the E11 mouse molar-forming mesenchyme and stage 23 chick mandibular mesenchyme. However, in contrast to BMPs, EGF did not induce Msx-1, Msx-2, and Bmp-4, but modulated the effects of BMPs on the expression of Msx-1 and Msx-2 in these mesenchymes. Our combined data suggest that BMP-7 is a component of the signaling network mediating epithelial-mesenchymal interactions during the initiation phase of odontogenesis and morphogenesis of the mandibular arch. (+info)
Cusp patterning defect in Tabby mouse teeth and its partial rescue by FGF.
(26/1158)
Tabby is a mouse mutant characterized by deficient development of the ectodermal organs: teeth, hair, and a subset of glands. Ectodysplasin, the protein encoded by the Tabby gene, was recently identified as a novel TNF-like transmembrane protein but little is known about its function. We have examined the Tabby tooth phenotype in detail by analysis of the adult and embryonic teeth. Tabby first molars had an obvious defect in cusp patterning as the number of cusps was reduced and the buccal and lingual cusps were joined. The disturbance in development was first visible morphologically in the bud stage molar. The primary enamel knot in a cap stage Tabby tooth expressed all enamel knot markers analyzed but was smaller than wild type and the first pair of developing secondary enamel knots was fused. We propose that the Tabby tooth phenotype is due to growth retardation during early stages of development which leads to reduced signaling from the primary enamel knot, followed by deficient growth of the dental epithelium and lack of formation of the last developing secondary enamel knots. The ectodysplasin transcripts were expressed in the outer enamel epithelium and dental lamina. When cultured in vitro Tabby bud/cap stage molars formed fewer cusps than wild-type controls. This phenotype was not rescued by exogenously added EGF despite the previously proposed link between Tabby and EGF. Instead FGF-10 partially restored morphogenesis and stimulated the development of additional tooth cusps in cultured Tabby molars. (+info)
Transcription factor Sp3 is essential for post-natal survival and late tooth development.
(27/1158)
Sp3 is a ubiquitously expressed transcription factor closely related to Sp1 (specificity protein 1). We have disrupted the mouse Sp3 gene by homologous recombination. Sp3-deficient embryos are growth retarded and invariably die at birth of respiratory failure. The cause for the observed breathing defect remains obscure since only minor morphological alterations were observed in the lung, and surfactant protein expression is indistinguishable from that in wild-type mice. Histological examinations of individual organs in Sp3(-/-) mice show a pronounced defect in late tooth formation. In Sp3 null mice, the dentin/enamel layer of the developing teeth is impaired due to the lack of ameloblast-specific gene products. Comparison of the Sp1 and Sp3 knockout phenotype shows that Sp1 and Sp3 have distinct functions in vivo, but also suggests a degree of functional redundancy. (+info)
Coinvasion of dentinal tubules by Porphyromonas gingivalis and Streptococcus gordonii depends upon binding specificity of streptococcal antigen I/II adhesin.
(28/1158)
Cell wall-anchored polypeptides of the antigen I/II family are produced by many species of oral streptococci. These proteins mediate adhesion of streptococci to salivary glycoproteins and to other oral microorganisms and promote binding of cells to collagen type I and invasion of dentinal tubules. Since infections of the root canal system have a mixed anaerobic bacterial etiology, we investigated the hypothesis that coadhesion of anaerobic bacteria with streptococci may facilitate invasive endodontic disease. Porphyromonas gingivalis ATCC 33277 cells were able to invade dentinal tubules when cocultured with Streptococcus gordonii DL1 (Challis) but not when cocultured with Streptococcus mutans NG8. An isogenic noninvasive mutant of S. gordonii, with production of SspA and SspB (antigen I/II family) polypeptides abrogated, was deficient in binding to collagen and had a 40% reduced ability to support adhesion of P. gingivalis. Heterologous expression of the S. mutans SpaP (antigen I/II) protein in this mutant restored collagen binding and tubule invasion but not adhesion to P. gingivalis or the ability to promote P. gingivalis coinvasion of dentin. An isogenic afimbrial mutant of P. gingivalis had 50% reduced binding to S. gordonii cells but was unaffected in the ability to coinvade dentinal tubules with S. gordonii wild-type cells. Expression of the S. gordonii SspA or SspB polypeptide on the surface of Lactococcus lactis cells endowed these bacteria with the abilities to bind P. gingivalis, penetrate dentinal tubules, and promote P. gingivalis coinvasion of dentin. The results demonstrate that collagen-binding and P. gingivalis-binding properties of antigen I/II polypeptides are discrete functions. Specificity of antigen I/II polypeptide recognition accounts for the ability of P. gingivalis to coinvade dentinal tubules with S. gordonii but not with S. mutans. This provides evidence that the specificity of interbacterial coadhesion may influence directly the etiology of pulpal and periapical diseases. (+info)
Widanelfarasia, a diminutive placental from the late Eocene of Egypt.
(29/1158)
The lower dentition of Widanelfarasia (new genus), a diminutive late Eocene placental from the Fayum Depression in Egypt, is described. Widanelfarasia exhibits a complex of features associated with incipient zalambdodonty and at least three unequivocal apomorphies [loss of P(1), an enlarged I(2) (relative to I(3)), and a basal cusp on I(2)], which provide weak support for its placement as a possible sister taxon of either a tenrecid-chrysochlorid clade or of solenodontids. The former hypothesis gains additional support from biogeographical evidence, but both scenarios are currently tenuous as Widanelfarasia is clearly not truly zalambdodont. Phylogenetic hypotheses positing affinities with tenrecids alone or chrysochlorids alone must invoke either convergent acquisition of zalambdodonty in these taxa or autapomorphic reversal in Widanelfarasia. Given these considerations, a relationship with more generalized taxa from the Laurasian Paleogene (e.g., geolabidids, nyctitheriids, leptictids) cannot yet be ruled out. Comparisons with other Paleogene Afro-Arabian forms are generally inconclusive. A relationship with the earlier Eocene Chambilestes from Tunisia-currently represented by a single specimen preserving P(4)-M(3)-seems possible based on the geometry and predicted occlusal relationships of these teeth, but cannot be confidently determined until these two taxa come to be represented by common diagnostic elements. Todralestes (late Paleocene, Morocco) exhibits general phenetic similarities to Widanelfarasia, but it is not yet known whether this taxon shares any of Widanelfarasia's unequivocal dental apomorphies. Pending the recovery of more informative material, we tentatively refer Widanelfarasia to Placentalia incertae sedis. Truly zalambdodont placentals remain conspicuously absent from the Paleogene of Afro-Arabia. (+info)
Dynamic Lunatic fringe expression is correlated with boundaries formation in developing mouse teeth.
(30/1158)
The formation of boundaries is a fundamental organizing principle during development. The Notch signalling pathway regulates this developmental patterning mechanism in many tissues. Recent data suggest that Notch receptors are involved in boundary determination during odontogenesis. It remains, however, uncertain if other components of the Notch pathway are also important for compartmental lineage restrictions in teeth. Here we report on the expression of the Lunatic fringe gene, which encodes a secreted signalling molecule regulating the Notch pathway, during the development of mouse teeth. Lunatic fringe is expressed in both epithelial and mesenchymal components of the developing molar. The expression pattern of Lunatic fringe in the epithelium is complementary to that of the Notch receptors. Lunatic fringe is asymmetrically expressed in the incisor epithelium during its antero-posterior rotation. This expression pattern defines the lingual comportment of the incisor epithelium whereas the labial comportment is defined by Notch2 expression. (+info)
Reiterative signaling and patterning during mammalian tooth morphogenesis.
(31/1158)
Mammalian dentition consists of teeth that develop as discrete organs. From anterior to posterior, the dentition is divided into regions of incisor, canine, premolar and molar tooth types. Particularly teeth in the molar region are very diverse in shape. The development of individual teeth involves epithelial-mesenchymal interactions that are mediated by signals shared with other organs. Parts of the molecular details of signaling networks have been established, particularly in the signal families BMP, FGF, Hh and Wnt, mostly by the analysis of gene expression and signaling responses in knockout mice with arrested tooth development. Recent evidence suggests that largely the same signaling cascade is used reiteratively throughout tooth development. The successional determination of tooth region, tooth type, tooth crown base and individual cusps involves signals that regulate tissue growth and differentiation. Tooth type appears to be determined by epithelial signals and to involve differential activation of homeobox genes in the mesenchyme. This differential signaling could have allowed the evolutionary divergence of tooth shapes among the four tooth types. The advancing tooth morphogenesis is punctuated by transient signaling centers in the epithelium corresponding to the initiation of tooth buds, tooth crowns and individual cusps. The latter two signaling centers, the primary enamel knot and the secondary enamel knot, have been well characterized and are thought to direct the differential growth and subsequent folding of the dental epithelium. Several members of the FGF signal family have been implicated in the control of cell proliferation around the non-dividing enamel knots. Spatiotemporal induction of the secondary enamel knots determines the cusp patterns of individual teeth and is likely to involve repeated activation and inhibition of signaling as suggested for patterning of other epithelial organs. (+info)
Linking development with generation of novelty in mammalian teeth.
(32/1158)
The evolution of mammalian teeth is characterized by the frequent and convergent evolution of new cusps. The evolution of new cusps can be linked to tooth development via population-level variation. This allows testing whether development increases the capacity to evolve, or evolvability, by facilitating and even directing morphological change. In a population sample of living seals, variation in cusp number of individual teeth is from three to five cusps, the variably present cusps being the shortest ones that also develop last. By factoring in recent evidence on development, I show that the variation in cusp number can be explained by a patterning cascade mode of cusp development that cumulatively increases and directs height variation in short cusps. The biased variation in seal tooth cusps supports the recognition of teeth as highly evolvable because only small developmental changes are needed to produce large changes in size and number of small cusps. This evolvability of tooth cusps may have facilitated the fast and independent acquisition of new cusps in mammalian evolution. In phylogenetic studies, small cusps may be unreliable as phylogenetic signals. Population level variation can be a powerful tool in testing and generating hypotheses in developmental evolution studies. (+info)