Molecular genetics of supernumerary tooth formation

Despite advances in the knowledge of tooth morphogenesis and differentiation, relatively little is known about the aetiology and molecular mechanisms underlying supernumerary tooth formation. A small number of supernumerary teeth may be a common developmental dental anomaly, while multiple supernumerary teeth usually have a genetic component and they are sometimes thought to represent a partial third dentition in humans. Mice, which are commonly used for studying tooth development, only exhibit one dentition, with very few mouse models exhibiting supernumerary teeth similar to those in humans. Inactivation of Apc or forced activation of Wnt/β(catenin signalling results in multiple supernumerary tooth formation in both humans and in mice, but the key genes in these pathways are not very clear. Analysis of other model systems with continuous tooth replacement or secondary tooth formation, such as fish, snake, lizard, and ferret, is providing insights into the molecular and cellular mechanisms underlying succesional tooth development, and will assist in the studies on supernumerary tooth formation in humans. This information, together with the advances in stem cell biology and tissue engineering, will pave ways for the tooth regeneration and tooth bioengineering.     

A novel mutation of adenomatous polyposis coli (APC) gene results in the formation of supernumerary teeth

Supernumerary teeth are teeth that are present in addition to normal teeth. Although several hypotheses and some molecular signalling pathways explain the formation of supernumerary teeth, but their exact disease pathogenesis is unknown. To study the molecular mechanisms of supernumerary tooth‐related syndrome (Gardner syndrome), a deeper understanding of the aetiology of supernumerary teeth and the associated syndrome is needed, with the goal of inhibiting disease inheritance via prenatal diagnosis. We recruited a Chinese family with Gardner syndrome. Haematoxylin and eosin staining of supernumerary teeth and colonic polyp lesion biopsies revealed that these patients exhibited significant pathological characteristics. APC gene mutations were detected by PCR and direct sequencing. We revealed the pathological pathway involved in human supernumerary tooth development and the mouse tooth germ development expression profile by RNA sequencing (RNA‐seq). Sequencing analysis revealed that an APC gene mutation in exon 15, namely 4292‐4293‐Del GA, caused Gardner syndrome in this family. This mutation not only initiated the various manifestations typical of Gardner syndrome but also resulted in odontoma and supernumerary teeth in this case. Furthermore, RNA‐seq analysis of human supernumerary teeth suggests that the APC gene is the key gene involved in the development of supernumerary teeth in humans. The mouse tooth germ development expression profile shows that the APC gene plays an important role in tooth germ development. We identified a new mutation in the APC gene that results in supernumerary teeth in association with Gardner syndrome. This information may shed light on the molecular pathogenesis of supernumerary teeth. Gene‐based diagnosis and gene therapy for supernumerary teeth may become available in the future, and our study provides a high‐resolution reference for treating other syndromes associated with supernumerary teeth.     

中国河南晚白垩世地层一枚可能属于重爪龙亚科(兽脚亚目:棘龙科)的牙齿化石(英文)

中国河南晚白垩世中段地层马家村组发现了一枚大型兽脚龙类牙齿。该牙牙体长,呈圆锥状,横断面卵圆形,沿长轴微向后缘弯曲,前后缘均有大量锯齿状突起,这些特征显示其很可能是重爪龙类牙齿。这可能代表了重爪龙类在亚洲地区的首次发现,也是该类恐龙在晚白垩世地层中的首现,由此表明重爪龙类在时间和地域分布上较之前研究观点更为广泛。综合棘龙科的化石形态学以及推知的生态学证据看,较之其他兽脚类,棘龙类化石记录很少,很可能意味该类动物数量确实稀少,造成这种现象的原因可能是其过分特化的身体形态。     

The epidemiology of supernumerary teeth and the associated molecular mechanism

Supernumerary teeth are common clinical dental anomalies. Although various studies have provided abundant information regarding genes and signaling pathways involved in tooth morphogenesis, which include Wnt, FGF, BMP, and Shh, the molecular mechanism of tooth formation, especially for supernumerary teeth, is still unclear. In the population, some cases of supernumerary teeth are sporadic, while others are syndrome-related with familial hereditary. The prompt and accurate diagnosis of syndrome related supernumerary teeth is quite important for some distinctive disorders. Mice are the most commonly used model system for investigating supernumerary teeth. The upregulation of Wnt and Shh signaling in the dental epithelium results in the formation of multiple supernumerary teeth in mice. Understanding the molecular mechanism of supernumerary teeth is also a component of understanding tooth formation in general and provides clinical guidance for early diagnosis and treatment in the future.     

A new weevil genus of the tribe Metrioxenini (Coleoptera: Belidae) in Eocene Baltic amber

A new genus, Succinometrioxena n. gen., and a new species, S. poinari n. sp. (Metrioxenini: Oxycoryninae), are described from Baltic amber. This new genus resembles the recent genus Wallacexena Legalov, 2009 but differs from it by the frons with horn-like tubercles on either side, the absence of a middle pronotal carina, teeth on the side of the pronotum, the anterior margin of the pronotum lacking teeth and two long carinae on the elytra. From the fossil genus Paltorhynchus Scudder, 1893 the present fossil differs by possessing a frons with horn-like tubercles on either side, the absence of a middle pronotal carina, teeth on the sides of the pronotum, two long carinae on the elytra and short temples. From the fossil genus Archimetrioxena Voss, 1953, the new genus differs by the frons with horn-like tubercles on either side, the absence of the two truncated elytral carinae, the sides of the pronotum with teeth, short temples and a larger body size.     

New information on cranial and dental features of the Triassic archosauriform reptile Euparkeria capensis

The course of the nasolacrimal duct, interdental plate morphology, and most details of tooth and denticle morphology have not previously been described in non–archosauriform reptilkes. Here I describe these details in the Triassic archosauriform Euparkeria capensis. The nasolacrimal canal opens orbitally via a pair of foramina between the lacrimal and prefrontal. The canal arches over the antorbital fenestra, as in archosaurs. The term ‘interdental unit’ is introduced for the unit composed of an interdental septum and its accompanying interdental plate. There is no demarcation between interdental plate and septum in E. capensis. The interdental units are heavily pitted on exposed surfaces. Like teeth, they are implanted in the dental groove and are separate from the surrounding bone and from each other. They are well positioned to serve as spacers between teeth, and to resist sagittal forces on teeth during prey capture. The teeth of E. capensis are labiolingually compressed, except for the nearly conical premaxillary teeth and mesialmost dentary tooth. Lateral teeth are serrated on mesial and distal keels. The denticles are low, rounded, and separated by grooves, and are slightly larger on the distal keel. Tooth morphology suggests carnivorous habits for Euparkeria.     

A tooth crown morphology framework for interpreting the diversity of primate dentitions

Variation in tooth crown morphology plays a crucial role in species diagnoses, phylogenetic inference, and the reconstruction of the evolutionary history of the primate clade. While a growing number of studies have identified developmental mechanisms linked to tooth size and cusp patterning in mammalian crown morphology, it is unclear (1) to what degree these are applicable across primates and (2) which additional developmental mechanisms should be recognized as playing important roles in odontogenesis. From detailed observations of lower molar enamel–dentine junction morphology from taxa representing the major primate clades, we outline multiple phylogenetic and developmental components responsible for crown patterning, and formulate a tooth crown morphology framework for the holistic interpretation of primate crown morphology. We suggest that adopting this framework is crucial for the characterization of tooth morphology in studies of dental development, discrete trait analysis, and systematics.     

经典Wnt信号通路在牙齿发育中的研究新进展

经典Wnt信号通路是参与胚胎及器官发育的四大信号传导途径之一,在牙齿发育中扮演了重要的角色。本文对其中的β-catenin,Left,Ape,Axin2这4个关键因子在牙齿发育中研究的新进展做了简要的概述：β-catenin在间充质中会调控多个信号,影响牙上皮和间充质相互作用;Left会和Tcf家族一道调控上皮细胞命运;Ape能抑制多余牙齿的形成;Axin2在牙晚期发育中影响牙本质的形成。通过这些因子的研究,希望人们能在牙齿再生等生物医学工程上有新的突破。     

Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation

The term "supernumerary teeth" describes production of more than the normal number of teeth in the primary or permanent dentitions. Their aetiology is not understood. Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist that plays important roles in the local regulation of BMP signaling by binding and neutralizing BMP activities, and also serves as a modulator of Wnt signaling. We report here that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor tooth. We confirmed that the USAG-1 expression is localized to the epithelium and mesenchyme of the rudimentary maxillary incisor tooth organ formation. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. Based upon these results, we conclude that USAG-1 controls the number of teeth in the maxillary incisor region by regulating apoptosis.     

Ontogeny of postcanine tooth form in the ferret,Mustela putorius (Carnivora: Mammalia), and the evolution of dental diversity within the mustelidae

This study describes dental development within the ferret, Mustela putorius, through study of the form of the carnassial teeth and the upper first molar at progressive growth stages. Primordial teeth were serially sectioned in sagittal and transverse planes and three-dimensional reconstructions of tooth primordia were generated using MacReco software. Regional growth of the crown and asynchronous maturation of the dental tissues were observed in each tooth. The upper carnassial blade develops early and the tooth increases in length rapidly. Lingual growth of the upper carnassial is less pronounced and the protocone and its surrounding region mature late. The lower carnassial blade develops early and the talonid is late to mature. Development of the upper first molar differs from carnassial development in the early emphasis upon transverse growth and reduced lengthwise expansion. The early development of the carnassial blades in the ferret is shared with other carnivores, and may reflect the functional significance of this feature. Later stages of tooth ontogeny differ among carnivoran taxa and the specialized morphology of ferret teeth results from an apparently truncated period of late tooth ontogeny. This suggests that carnivoran species may share a common path of early development that specifies the ontogeny of homologous tooth features and that in later stages developmental differences result in species-specific tooth forms. J. Morphol. 237:69–90, 1998. © 1998 Wiley-Liss, Inc.     

Splitting placodes: effects of bone morphogenetic protein and Activin on the patterning and identity of mouse incisors

SUMMARY The single large rodent incisor in each jaw quadrant is evolutionarily derived from a mammalian ancestor with many small incisors. The embryonic placode giving rise to the mouse incisor is considerably larger than the molar placode, and the question remains whether this large incisor placode is a developmental requisite to make a thick incisor. Here we used in vitro culture system to experiment with the molecular mechanism regulating tooth placode development and how mice have thick incisors. We found that large placodes are prone to disintegration and formation of two to three small incisor placodes. The balance between one large or multiple small placodes was altered through the regulation of bone morphogenetic protein (BMP) and Activin signaling. Exogenous Noggin, which inhibits BMP signaling, or exogenous Activin cause the development of two to three incisors. These incisors were more slender than normal incisors. Additionally, two inhibitor molecules, Sostdc1 and Follistatin, which regulate the effects of BMPs and Activin and have opposite expression patterns, are likely to be involved in the incisor placode regulation in vivo. Furthermore, inhibition of BMPs by recombinant Noggin has been previously suggested to cause a change in the tooth identity from the incisor to the molar. This evidence has been used to support a homeobox code in determining tooth identity. Our work provides an alternative interpretation, where the inhibition of BMP signaling can lead to splitting of the large incisor placode and the formation of partly separate incisors, thereby acquiring molar‐like morphology without a change in tooth identity.     

A new fossil species of the extinct tribe Mimoplatycini Kazantsev, 2013 (Coleoptera Cantharidae)

A new fossil species from the Eocene Baltic amber of the extinct tribe Mimoplatycini Kazantsev, 2013 (Cantharidae Malthininae), is illustrated and described here. Mimoplatycis marchettii sp. nov. is characterized by a transverse but interrupted carina in the middle of pronotum. The tribe is known from Baltic and Rovno amber, and the pronotum with carinae similar to Lycidae could be interpreted as mimicry. The pronotal shape is here indicated as a diagnostic character of the species level.     

Convergent dental adaptations in the serrations of hypercarnivorous synapsids and dinosaurs

Theropod dinosaurs are well known for having a ziphodont dentition: serrated, blade-shaped teeth that they used for cutting through prey. Serrations along the carinae of theropod teeth are composed of true denticles, a complex arrangement of dentine, enamel, and interdental folds. This structure would have supported individual denticles and dissipated the stresses associated with feeding. These particular serrations were previously thought to be unique to theropod dinosaurs and some other archosaurs. Here, we identify the same denticles and interdental folds forming the cutting edges in the teeth of a Permian gorgonopsian synapsid, extending the temporal and phylogenetic distribution of this dental morphology. This remarkable instance of convergence not only represents the earliest record of this adaptation to hypercarnivory but also demonstrates that the first iteration of this feature appeared in non-mammalian synapsids. Comparisons of tooth serrations in gorgonopsians with those of earlier synapsids and hypercarnivorous mammals reveal some gorgonopsians acquired a complex tissue arrangement that differed from other synapsids.     

Patterning during somatic embryogenesis in Scots pine in relation to polar auxin transport and programmed cell death

Somatic embryogenesis is a useful tool to propagate conifers vegetatively. However, a major limitation in many pine species is the low quality of cotyledonary somatic embryos. The aim of this study has been to elucidate the developmental pathway of somatic embryos in Scots pine (Pinus sylvestris), to identify deviations from the normal pathway and to identify processes that might disturb normal development. Initially we compared the developmental pathway of somatic embryogenesis in representative cell lines yielding cotyledonary embryos with normal and abnormal morphology. Early embryos carrying suspensor cells in excess of the normal number (supernumerary) were more frequent in cell lines giving rise to abnormal cotyledonary embryos. In this study we show that the frequency of early somatic embryos with supernumerary suspensor cells increased after treatment with the auxin transport inhibitor 1-N-naphtylphthalamic acid (NPA). Furthermore, the yield of developing embryos increased significantly after treatment with the antiauxin 2-(4-chlorophenoxy)-2-methylpropionic acid (PCIB), but the morphology of the embryos was not affected. The number of cells undergoing PCD was analyzed using a TUNEL-assay. The frequency of TUNEL-positive cells was high both in proliferating cultures and during differentiation of early somatic embryos. However, the pattern of TUNEL-positive cells was similar in normal somatic embryos and in embryos with supernumerary suspensor cells. Together our results suggest that the presence of supernumerary suspensor cells in early somatic embryos of Scots pine is caused by disturbed polar auxin transport and results in aberrant embryo development.     

Two-hit model for sporadic congenital anomalies in mice with the disorganization mutation.

Congenital anomalies have complex etiologies involving both genetic and nongenetic components. Many are sporadic, without obvious evidence for heritability. An important model for these anomalies is a mutation in laboratory mice that is called "disorganization" (Ds), which functions as a variable autosomal dominant and leads to a wide variety of congenital anomalies involving many developmental processes and systems. Variable expressivity, asymmetrical manifestations, and low penetrance suggest that somatic events determine the location and nature of these anomalies. A statistical analysis suggests that occurrence of anomalies in mice with the Ds mutation follows a Poisson distribution. These results suggest that congenital anomalies in mice with the Ds mutation occur independently of each other. We propose that Ds causes a heritable predisposition to congenital anomalies and that Ds and appropriate somatic events combine to compromise normal development. We also propose that some sporadic, nonheritable congenital anomalies involve somatic mutations at Ds-like loci. Ds may therefore serve not only as a model for developmental anomalies in cell fate and pattern formation but also for complex developmental traits showing variable expressivity, low penetrance, and sporadic occurrence in mice and humans.     

Abnormal Fossil Upper Molar of Pongo from Thailand: Quaternary Climatic Changes in Southeast Asia as a Possible Cause

We interpret an unusual left M ³ attributed to Pongo from the Late Middle Pleistocene of Thailand to be an abnormal tooth rather than a supernumerary molar. Its peculiar morphology cannot be related to classical known causes that affect the dental germ: Gemination, schizodontia, synodontia. The ontogenic mechanism that might have led to the morphology of the tooth perhaps reflects stress related to a phase of marked climatic changes during the Late Middle Pleistocene in Southeast Asia.     

Epiprofin/Sp6: a new player in the regulation of tooth development

Odontogenesis is governed by a complex network of intercellular signaling events between the dental epithelium and mesenchyme. This network leads to the progressive determination of tooth shape, and to the differentiation of these tissues into enamel-producing ameloblasts and dentin-producing odontoblasts respectively. Among the main signaling pathways involved in the regulation of tooth development, Bone Morphogenetic Protein (BMP), Sonic hedgehog (Shh) and Wingless-type MMTV integration site (Wnt) pathways have been reported to play significant roles. Recently, the phenotype of mice deficient in Epiprofin/Sp6 (Epfn) has been found to present striking dental abnormalities, including a complete lack of differentiated ameloblasts and consequently no enamel, highly altered molar cusp patterns and the formation of multiple supernumerary teeth. In this article, we review the interaction of Epfn with the BMP, Shh and Wnt pathways in the regulation of tooth development, based on the data obtained from the study of several genetically modified mice.     

Macroscopic and microscopic analyses of linear enamel hypoplasia in Plio-Pleistocene South African hominins with respect to aspects of enamel development and morphology

This study uses macroscopic and microscopic methods to analyze the expression of linear enamel hypoplasia (LEH) in Plio-Pleistocene South African hominins. LEH is a developmental defect of enamel that is used in many anthropological contexts as a physiological stress indicator. Previous research has not settled the question as to whether differences in LEH expression exist between Paranthropus and Australopithecus and if they exist, to what extent these differences might be explained simply by taxonomic differences in enamel development and morphology rather than by differential stress experience. In this study, the analysis of LEH is conducted with respect to differences between Paranthropus and Australopithecus in aspects of enamel development and morphology that are thought to influence LEH expression. Two factors impacting LEH expression are considered: the duration of enamel formation, and the spacing of perikymata. It is predicted that if the first factor strongly influences the expression of LEH, then there should be fewer defects per tooth in Paranthropus because of its abbreviated crown formation spans (and fast extension rates) relative to Australopithecus. It is also predicted that because Australopithecus has more densely packed perikymata in comparable regions of the crown than Paranthropus, this taxon should, on average, have narrower defects than Paranthropus. To address these questions, 200 Australopithecus and 137 Paranthropus teeth were examined for LEH, and the analysis of defect width with respect to perikymata spacing was conducted on tooth impressions examined under a scanning electron microscope using INCA (Oxford Instruments) measurement software. Data support the first prediction: Australopithecus does have significantly more defects per canine tooth than Paranthropus. Data do not support the second prediction in large part because several Australopithecus specimens have wide groove defects in which perikymata are not visible and enamel is irregular. Such wide grooves are not predicted by perikymata spacing such that alternative explanations, including taxonomic differences in ameloblast sensitivity and the duration/severity of disruptions to enamel growth, must be considered.