Homology,homoplasy and cusp variability at the enamel–dentine junction of hominoid molars

Evolutionary studies of mammalian teeth have generally concentrated on the adaptive and functional significance of dental features, whereas the role of development on phenotypic generation and as a source of variation has received comparatively little attention. The present study combines an evolutionary biological framework with state‐of‐the‐art imaging techniques to examine the developmental basis of variation of accessory cusps. Scholars have long used the position and relatedness of cusps to other crown structures as a criterion for differentiating between developmentally homologous and homoplastic features, which can be evaluated with greater accuracy at the enamel–dentine junction (EDJ). Following this approach, we collected digital models of the EDJ and outer enamel surface of more than 1000 hominoid teeth to examine whether cusp 5 of the upper molars (UM C5) and cusps 6 and 7 of the lower molars (LM C6 and LM C7) were associated each with a common developmental origin across species. Results revealed that each of these cusps can develop in a variety of ways, in association with different dental tissues (i.e. oral epithelium, enamel matrix) and dental structures (i.e. from different cusps, crests and cingula). Both within and between species variability in cusp origin was highest in UM C5, followed by LM C7, and finally LM C6. The lack of any species‐specific patterns suggests that accessory cusps in hominoids are developmentally homoplastic and that they may not be useful for identifying phylogenetic homology. An important and unanticipated finding of this study was the identification of a new taxonomically informative feature at the EDJ of the upper molars, namely the post‐paracone tubercle (PPT). We found that the PPT was nearly ubiquitous in H. neanderthalensis and the small sample of Middle Pleistocene African and European humans (MPAE) examined, differing significantly from the low frequencies observed in all other hominoids, including Pleistocene and recent H. sapiens. We emphasize the utility of the EDJ for human evolutionary studies and demonstrate how features that look similar at the external surface may be the product of different developmental patterns. This study also highlights the importance of incorporating both developmental and morphological data into evolutionary studies in order to gain a better understanding of the evolutionary significance of dental and skeletal features.     

The presence of accessory cusps in chimpanzee lower molars is consistent with a patterning cascade model of development

Tooth crown morphology is of primary importance in fossil primate systematics and understanding the developmental basis of its variation facilitates phenotypic analyses of fossil teeth. Lower molars of species in the chimp/human clade (including fossil hominins) possess between four and seven cusps and this variability has been implicated in alpha taxonomy and phylogenetic systematics. What is known about the developmental basis of variation in cusp number – based primarily on experimental studies of rodent molars – suggests that cusps form under a morphodynamic, patterning cascade model involving the iterative formation of enamel knots. In this study we test whether variation in cusp 6 (C6) presence in common chimpanzee and bonobo lower molars (n = 55) is consistent with predictions derived from the patterning cascade model. Using microcomputed tomography we imaged the enamel‐dentine junction of lower molars and used geometric morphometrics to examine shape variation in the molar crown correlated with variation in C6 presence (in particular the size and spacing of the dentine horns). Results indicate that C6 presence is consistent with predictions of a patterning cascade model, with larger molars exhibiting a higher frequency of C6 and with the location and size of later‐forming cusps correlated with C6 variation. These results demonstrate that a patterning cascade model is appropriate for interpreting cusp variation in Pan and have implications for cusp nomenclature and the use of accessory cusp morphology in primate systematics.     

Quantification of dentine shape in anthropoid primates

The external shape and thickness of the enamel component of primate molars have been employed extensively in phylogenetic studies of primate relationships. The dentine component of the molar crown also has been suggested to be indicative of phylogenetic relationships, but few studies have quantified dentine morphology in order to evaluate this possibility. To explore the utility of dentine shape as an indicator of phylogenetic affinity, a two-dimensional geometric morphometric analysis (EDMA-II) was performed using nine homologous land-marks on a sample of sectioned maxillary molars of extant ceboid, cercopithecoid, and hominoid primates. Results indicate that dentine shape (the configuration of the enamel-dentine junction, or EDJ) can distinguish taxa at every taxonomic level examined, including superfamilies, subfamilies, and closely related genera and species. This supports the idea that dentine morphology may be useful for phylogenetic studies. It is further suggested that the morphology of the EDJ may be more conservative than enamel morphology, and perhaps better-suited to phylogenetic studies. Among the samples studied, cercopithecoid primates have a unique dentine shape, and it is suggested that the development of bilophodont molars may be related to the distinctive EDJ configuration in cercopithecoids.     

Do Mid‐Crown Enamel Formation Front Angles Reflect Factors Linked to the Pace of Primate Growth and Development?

Enamel formation front (EFF) angles represent the leading edge of enamel matrix secretion at particular points in time. These angles are influenced by rates of enamel extension (the rates at which tooth crowns grow in height), rates of enamel matrix secretion and the angles that prisms make with the enamel‐dentine junction. Previous research suggests, but has not yet established, that these angles reflect aspects of primate biology related to their pace of growth and development, most notably brain and body size. The present study tested this possibility on histological sections using phylogenetically‐controlled and Bonferroni‐corrected analyses spanning a broad taxonomic range. Ten species were represented in the analysis of anterior teeth; 17 in the analysis of posterior (postcanine) teeth (with varying sample sizes). Also, tested was the relationship of EFF angles to striae of Retzius periodicity (long period growth rhythms in enamel) and degree of folivory, as both factors are related to primate developmental rates. Finally, several analyses were conducted to investigate whether tooth size (operationalized as EDJ length) might mediate these relationships. Central results are as follows: (1) Relationships between EFF angles and brain weight (anterior teeth) and between EFF angles and body mass (anterior and posterior teeth) are statistically significant and (2) Mid‐crown EFF angles are not statistically significantly related to EDJ lengths. These results suggest that tooth size does not mediate relationships between EFF angles and brain weight/body mass and are discussed with respect to underlying enamel growth variables (especially rates of enamel extension and secretion). Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:125–139, 2018. © 2017 Wiley Periodicals, Inc.     

Exploring metameric variation in human molars: a morphological study using morphometric mapping

Human molars exhibit a type of metameric variation, which is the difference in serially repeated morphology within an organism. Various theories have been proposed to explain how this variation is brought about in the molars. Actualistic data that support the theories, however, are still relatively scarce because of methodological limitations. Here we propose new methods to analyse detailed tooth crown morphologies. We applied morphometric mapping to the enamel–dentine junction of human maxillary molars and examined whether odontogenetic models were adaptable to human maxillary molars. Our results showed that the upper first molar is phenotypically distinct among the maxillary molars. The average shape of the upper first molar is characterized by four well‐defined cusps and precipitous surface relief of the occlusal table. On the other hand, upper third molar is characterized by smooth surface relief of the occlusal table and shows greater shape variation and distinct distribution patterns in morphospace. The upper second molar represents an intermediate state between first and third molar. Size‐related shape variation was investigated by the allometric vector analysis, and it appeared that human maxillary molars tend to converge toward the shape of the upper first molar as the size increases. Differences between the upper first molar and the upper second and third molar can thus be largely explained as an effect of allometry. Collectively, these results indicate that the observed pattern of metameric variation in human molars is consistent with odontogenetic models of molar row structure (inhibitory cascade model) and molar crown morphology (patterning cascade model). This study shows that morphometric mapping is a useful tool to visualize and quantify the morphological features of teeth, which can provide the basis for a better understanding of tooth evolution linking morphology and development.     

Gender-based differences in the shape of the human corpus callosum are associated with allometric variations

The corpus callosum displays considerable morphological variability between individuals. Although some characteristics are thought to differ between male and female brains, there is no agreement regarding the source of this variation. Biomedical imaging and geometric morphometrics have provided tools to investigate shape and size variation in terms of integration and correlation. Here we analyze variations at the midsagittal outline of the corpus callosum in a sample of 102 young adults in order to describe and quantify the pattern of covariation associated with its morphology. Our results suggest that the shape of the corpus callosum is characterized by low levels of morphological integration, which explains the large variability. In larger brains, a minor allometric component involves a relative reduction of the splenium. Small differences between males and?females are associated with this allometric pattern, induced primarily by size variation rather than gender-specific characteristics.     

Safe Casting and Reliable Cusp Reconstruction Assisted by Micro-Computed Tomographic Scans of Fossil Teeth

Dental replicas are frequently utilized in paleoanthropological studies of perikymata and enamel hypoplasia. However, fossil teeth are often fragile and worn, causing two problems: (1) the risk of damage by removing enamel fragments when impression-making material is separated from the fossil tooth surface, and (2) the need to reconstruct worn portions of the crown to assess perikymata number, distribution, and hypoplasia timing. This study presents the advantages of μCT data of canines and lateral incisors for (1) detecting cracks along the enamel-dentine junction (EDJ) which could cause damage when casting, and (2) reliably and non-destructively reconstructing worn or broken cusps. Fragile teeth of Homo naledi, Miocene, and Pleistocene specimens were μCT-scanned: 2D virtual sections and 3D models allowed for inspecting crack pattern beyond the external surface and 2D virtual sections were used to digitally reconstruct cusp tips (only Homo naledi). Micro-CT scans allowed cracks running along the EDJ and communicating with radial cracks in the enamel to be identified prior to casting. Cusp reconstructions using μCT data were conducted as precisely as when using thin-sections or photographs, and with high intra- and inter-observer agreement, while preserving the original specimen and affording numerous planes of virtual section. When available, μCT data should be inspected prior to tooth casting to exclude teeth that show a pattern of cracks that could lead to damage. Virtual sections allow for accessible, reliable, and non-destructive cusp reconstructions that may be used for developmental (e.g., perikymata and enamel hypoplasia) or enamel thickness studies. Anat Rec, 302:1516–1535, 2019. © 2018 American Association for Anatomy     

Craniofacial variability and morphological integration in mice susceptible to cleft lip and palate

A/WySnJ mice are an inbred strain that develops cleft lip with or without cleft palate (CL/P) with a frequency of 25-30% and a predominantly unilateral expression pattern. As in humans, the pattern of incomplete penetrance, and variable and frequent unilateral expression suggests a role for altered regulation of variability (developmental stability, canalization and developmental integration) during growth. We compared both mean and variability parameters for craniofacial shape and size among A/WySnJ mice, a strain that does not develop CL/P (C57BL/6J) and their F1 cross. We show that adult A/WySnJ mice that do not express cleft lip exhibit decreased morphological integration of the cranium and that the co-ordination of overall shape and size variation is disrupted compared with both C57BL/6J mice and the F1 cross. The decrease in integration is most pronounced in the palate and face. The absence of this pattern in the F1 cross suggests that it is determined by recessive genetic factors. By contrast, the shape differences between the strains, which are thought to predispose A/WySnJ mice to CL/P, show a range of dominance which suggests a polygenic basis. We suggest that decreased integration of craniofacial growth may be an aetiological factor for CL/P in A/WySnJ mice.     

Effect of Down syndrome on the dimensions of dental crowns and tissues

Abnormal growth in Down syndrome (DS) is reflected by variable reduction in size and simplification in form of many physical traits. This study aimed to compare the thickness of enamel and dentine in deciduous and permanent mandibular incisor teeth between DS and non‐DS individuals and to clarify how these tissues contribute to altered tooth size in DS. Sample groups comprised 61 mandibular incisors (29 permanent and 32 deciduous) from DS individuals and 55 mandibular incisors (29 permanent and 26 deciduous) from non‐DS individuals. Maximum mesiodistal and labiolingual crown dimensions were measured initially, then the crowns were sectioned midsagittally and photographed using a stereomicroscope. Linear measurements of enamel and dentine thickness were obtained on the labial and lingual surfaces of the crowns, together with enamel and dentine–pulp areas and lengths of the dentino‐enamel junction. Reduced permanent crown size in DS was associated with a reduction in both enamel and dentine thickness. After adjustments were made for tooth size, DS permanent incisors had significantly thinner enamel than non‐DS permanent teeth. The DS permanent teeth also exhibited significant differences in shape and greater variability in dimensions than the non‐DS permanent teeth. Crown dimensions of deciduous incisors were similar in size or larger in DS compared with non‐DS deciduous teeth. Enamel and dentine thicknesses of the deciduous teeth were similar in DS and non‐DS individuals. The findings indicate that growth retardation in DS reduces both enamel and dentine deposition in the permanent incisors but not in the earlier‐forming deciduous predecessors. The results are also consistent with the concept of amplified developmental instability for dental traits in DS. Am. J. Hum. Biol. 13:690–698, 2001. © 2001 Wiley‐Liss, Inc.     

Interproximal contact hypoplasia in primary teeth: A new enamel defect with anthropological and clinical relevance

This study reports the prevalence, distribution, and expression of enamel defects in a sample of primary teeth (n = 225) from a prehistoric site in western India (1400–700 BC). Five enamel surfaces of individual, isolated primary teeth were observed for surface defects using a binocular stereomicroscope with variable power of magnification (8–20×). Standards for evaluating dental enamel defects (DDE) recommended by the Fédération Dentaire International (FDI) were employed. Details of defect expression were also recorded, including size, shape, and surface of tooth crown affected. Hypoplastic enamel defects were observed in 28% of teeth, but the distribution and expression of defects was not random. More than 50% of canine teeth had hypoplastic defects (HD); incisors and molar teeth exhibited far fewer HD. The buccal surface of canines was the most commonly affected crown surface. Areas of missing enamel were also common on the mesial and distal surfaces of canines and incisors and on the mesial surface of molar teeth. The high frequency of enamel defects found on interproximal crown surfaces warrants a label, and the name interproximal contact hypoplasia (IPCH) is proposed. Linear enamel hypoplasia (LEH) was absent from this primary dental sample. IPCH is more frequent in mandibular than in maxillary teeth, but no side preference was detected. In canine teeth, buccal hypoplasias (localized hypoplasia of primary canines; LHPC) were not positively correlated with interproximal hypoplastic defects. The etiology of IPCH may involve mesial compaction of developing teeth due to slow longitudinal growth of the jaws. Episodic bone remodeling results in ephemeral fenestrae in the mesial and distal walls of the dental crypt permitting tooth–tooth contact and disruption of amelogenesis. IPCH prevalence decreases across the subsistence transition from sedentary Early Jorwe agriculturalists to seminomadic Late Jorwe hunters and foragers, but the difference is not statistically significant. This may be due to underrepresentation of mandibular teeth in the sample. Am. J. Hum. Biol. 11:718–734, 1999. © 1999 Wiley-Liss, Inc.     

The impact of artificial selection on morphological integration in the appendicular skeleton of domestic horses

The relationships between the different component parts of organisms, such as the sharing of common development or function, produce a coordinated variation between the different traits. This morphological integration contributes to drive or constrain morphological variation and thus impacts phenotypic diversification. Artificial selection is known to contribute significantly to phenotypic diversification of domestic species. However, little attention has been paid to its potential impact on integration patterns. This study explores the patterns of integration in the limb bones of different horse breeds, using 3D geometric morphometrics. The domestic horse is known to have been strongly impacted by artificial selection, and was often selected for functional traits. Our results confirm that morphological integration among bones within the same limb is strong and apparently partly produced by functional factors. Most importantly, they reveal that artificial selection, which led to the diversification of domestic horses, impacts covariation patterns. The influence of selection on the patterns of covariation varies along the limbs and modulates bone shape, likely due to a differential ligament or muscle development. These results highlight that, in addition to not being constrained by a strong morphological integration, artificial selection has modulated the covariation patterns according to the locomotor specificities of the breeds. More broadly, it illustrates the interest in studying how micro‐evolutionary processes impact covariation patterns and consequently contribute to morphological diversification of domestic species.     

Characterization of short-period and long-period incremental markings in porcine enamel and dentine—Results of a fluorochrome labelling study in wild boar and domestic pigs

Mammalian dental hard tissues exhibit incremental markings that reflect the periodic variation of appositional growth rates. In order to use these markings to characterize dental growth processes and to infer life-history traits, an unequivocal identification of their periodicities is required. We performed a fluorochrome labelling study on forming enamel and dentine in molar teeth of wild boar and domestic pigs to establish the periodicity and temporal correspondence of incremental markings in enamel and dentine. The dominant incremental markings in enamel (laminations) and dentine (von Ebner lines) recorded in the pig teeth are of a daily nature. In addition, long-period incremental markings with a periodicity of 2 days were recorded in enamel (striae of Retzius) and dentine (Andresen lines). The 2-day growth rhythm was also expressed at the lateral crown surface, as evidenced by the pattern of perikymata. In enamel, also markings with a sub-daily periodicity, representing an ultradian growth rhythm, were observed. Our study provides experimental evidence for the periodicity of incremental markings in porcine enamel and dentine. The findings correct previous misconceptions on incremental markings in dental hard tissues of pigs and other ungulates that had led to erroneous conclusions regarding crown formation parameters.     

Dental Defects as a Potential Indicator of Chronic Malnutrition in a Population of Fallow Deer (Dama dama) from Northwestern Germany

We studied enamel defects in mandibular cheek teeth of fallow deer from an enclosed population that had grown far beyond the carrying capacity of its habitat. Macroscopic inspection revealed a high frequency of pathological enamel alterations in the permanent premolars and the third molar, which form late during dental development, while earlier forming teeth (deciduous premolars and first molar) were generally not affected. Macroscopic enamel alterations comprised opacity and posteruptive discoloration, loss of occlusal enamel ridges, and presence of enamel surface lesions. Backscattered electron imaging in the SEM revealed a marked hypomineralization and related increased porosity of the outer compared to the central and inner enamel portions in the affected teeth. In contrast, the enamel of the unaffected first molars showed a homogeneous high degree of mineralization. Microindentation hardness testing demonstrated a significantly reduced and highly variable hardness of the outer enamel of the affected teeth. The recorded enamel alterations are indicative of a disturbance of enamel maturation. Based on findings of experimental studies by other authors that explored the effects of dietary deficiencies on the mineralization of dental hard tissues in different mammal species, we suggest a dietary calcium deficiency as the cause of the observed pathological enamel changes in the fallow deer. The supposed calcium deficiency only affected teeth whose crown mineralization takes place after weaning, while the deciduous premolars and the first molar, whose crown formation occurs prenatally or during the early postnatal period of intense milk feeding, were unaffected. Anat Rec, 299:1409–1423, 2016. © 2016 Wiley Periodicals, Inc.     

Immunocytochemical demonstration of nerve growth factor receptor (NGF-R) in developing human fetal teeth

Evidence is accumulating that nerve growth factor receptor (NGF-R or p75^NGFR) can mediate cell growth and differentiation of non-neuronal cells. NGF-R expression was studied in developing teeth of human embryos and fetuses between the 6th and 18th weeks of gestation, using a monoclonal mouse-anti-human NGFR antibody. In contrast to earlier findings in rodents, the NGF-R expression of the human dental papilla was found to be transient. NGF-R was present in the condensing ecto-mesenchymal cells of the dental papilla in the early cap stage tooth germ. In later developmental stages, a shift of the NGF-R expression from the papilla to the cytoplasmic membrane of the inner enamel epithelium (IEE) was demonstrated. As in rodent odontogenesis, the NGF-R immunoreactivity of the IEE remained until the odontoblasts started secretion of predentinal matrix in the late bell state. The mitotic activity in the IEE was detected by an antibody against proliferating cell nuclear antigen (PCNA) and showed that the NGFR expression of the IEE decreased as the cell proliferation ceased. We propose that NGF-R may, be involved in differentiational and/or proliferative events of human odontogenesis.     

Mechanical properties and microstructure of hypomineralised enamel of permanent teeth

Isolated enamel defects are commonly seen in first permanent molar teeth but there has been little work on the physical and morphological composition of affected molars. The aim of this study was to determine the mechanical and morphological properties of hypomineralised first permanent molar teeth, utilising the Ultra-Micro-Indentation System (UMIS) and scanning electron microscope, respectively. Further investigations using Energy Dispersive X-ray Spectrometery (EDS), Back Scatter Electron (BSE) Imaging, and X-ray diffraction were employed to attempt to determine the chemical composition, mineral content and crystalline structure of the hypomineralised tissue, respectively, of eight first permanent molars with severe enamel hypomineralisation. The hardness and modulus of elasticity were found to be statistically significantly lower (0.53+/-0.31 and 14.49+/-7.56 GPa, respectively) than normal enamel (3.66+/-0.75 and 75.57+/-9.98 GPa, respectively). Although the fractured surface of the hypomineralised enamel was significantly more disorganised and the relative mineral content was reduced by approximately 5% in comparison to sound enamel, the mineral phase and Ca/P ratio was similar in hypomineralised and sound enamel. The dramatic reduction in the mechanical properties of first permanent molar teeth has ramifications when clinicians are choosing restorative materials to restore the defects. The reason for the dramatic reduction in mechanical properties of hypomineralised first permanent molar teeth is at present unknown.     

A first glimpse at the influence of body mass in the morphological integration of the limb long bones: an investigation in modern rhinoceroses

The appendicular skeleton of tetrapods is a particularly integrated structure due to the shared developmental origin or similar functional constraints exerted on its elements. Among these constraints, body mass is considered strongly to influence its integration but its effect on shape covariation has rarely been addressed in mammals, especially in heavy taxa. Here, we propose to explore the covariation patterns of the long bones in heavy animals and their link to body mass. We investigate the five modern rhinoceros species, which display an important range of bodyweight. We used a 3D geometric morphometric approach to describe the shape covariation of the six bones composing the stylopodium and zeugopodium both among and within species. Our results indicate that the appendicular skeleton of modern rhinos is a strongly integrated structure. At the interspecific level, the shape covariation is roughly similar between all pairs of bones and mainly concerns the muscular insertions related to powerful flexion and extension movements. The forelimb integration appears higher and more related to body mass than that of the hind limb, suggesting a specialization for weight support. The integration of the stylopodium elements does not seem to relate to body mass in our sample, which suggests a greater effect of shared developmental factors. Conversely, the covariation of the zeugopodium bones seems more associated with body mass, particularly for the radius-ulna pair. The fibula appears poorly integrated with other bones, especially within non-Rhinoceros species, which may represent a case of parcellation due to a functional dissociation between the hind limb bones. The exploration of the integration patterns at the intraspecific level also highlights a more prominent effect of age over individual body mass on shape covariation within C. simum. This study lends support to previous hypotheses indicating a link between high body mass and high integration level.     

Effect of eda Loss of Function on Upper Jugal Tooth Morphology

The Tabby/eda mice, which bear a loss of function mutation for the eda (ectodysplasinA) gene, are known to display developmental anomalies in organs with an ectodermal origin. Although the lower jugal (cheek) teeth of Tabby/eda mice have been extensively studied, upper teeth have never been investigated in detail. However, this may help us to further understand the function of the eda gene in tooth development. In this work, the shape and size of both the crown and the radicular system were studied in the Tabby/eda mice upper jugal teeth. To deal with the high morphological variability, we defined several morphotypes based on cusp numbers and position. Statistical tests were then performed within and between the different morphotypes to test the correlation between tooth size and morphology. Our analysis reveals that, as in lower teeth, eda is necessary to segment the dental lamina into three teeth with the characteristic size and proportions of the mouse. Nevertheless, since strong effects are observed in heterozygous upper teeth while lower are only mildly affected, it seems that the upper jaw is more sensitive than the lower jaw to the loss of eda function. Modifications in cusp number and the abnormal crown size of the teeth are clearly linked, and our results indicate a role of eda in cusp patterning. Moreover, we found that the Tabby mutation induces variations in the dental root pattern, sometimes associated with hypercementosis, suggesting a newly uncovered role played by eda in root patterning and formation. Anat Rec, 2009. © 2008 Wiley‐Liss, Inc.     

Shape covariation between the craniofacial complex and first molars in humans

The occurrence of mutual genetic loci in morphogenesis of the face and teeth implies shape covariation between these structures. However, teeth finalize their shape at an early age, whereas the face grows and is subjected to environmental influences for a prolonged period; it is therefore conceivable that covariation might modulate with age. Here we investigate the extent of this covariation in humans by measuring the 3D shape of the occlusal surface of the permanent first molars and the shape of the craniofacial complex from lateral radiographs, at two maturations stages. A sample of Greek subjects was divided into two groups (110 adult, 110 prepubertal) with equally distributed gender. The occlusal surfaces of the right first molars were 3D scanned from dental casts; 265 and 274 landmarks (including surface and curve semilandmarks) were digitized on the maxillary and mandibular molars, respectively. The corresponding lateral cephalometric radiographs were digitized with 71 landmarks. Geometric morphometric methods were used to assess shape variation and covariation. The vertical dimension of the craniofacial complex was the main parameter of shape variation, followed by anteroposterior deviations. The male craniofacial complex was larger (4.0–5.7%) and was characterized by a prominent chin and clockwise rotation of the cranial base (adult group only). Allometry was weak and statistically significant only when examined for the sample as a whole (percent variance explained: 2.1%, P = 0.0002). Covariation was statistically significant only between the lower first molar and the craniofacial complex (RV = 14.05%, P = 0.0099, and RV = 12.31%, P = 0.0162, for the prepubertal and adult groups, respectively). Subtle age‐related covariation differences were noted, indicating that environmental factors may influence the pattern and strength of covariation. However, the main pattern was similar in both groups: a class III skeletal pattern (relative maxillary retrusion and mandibular protrusion), hyperdivergency, forward rotation of the posterior cranial base and upward rotation of the anterior cranial base were associated with mesiodistal elongation of the lower molars and height reduction of their distal cusps. This pattern mimics phylogeny in humans, where flexion and counterclockwise rotation of the cranial base, considered advantageous to survival, co‐occur with tooth reductions that cannot be easily explained in evolutionary terms. The similarity of the phylogenetic and covariation patterns seems to support the pleiotropic gene hypothesis.     

A spontaneous mutation: amelogenesis imperfecta with cysts in rats

Amelogenesis imperfecta (AI) is an inherited dental disease of enamel formation in humans, and there are various phenotypes due to the combination of enamel quality and quantity. We encountered four female IGS rats with spontaneous AI including odontogenic cysts in the incisor teeth. Histopathologically, in the incisors of the rats, the enamel organ was disorganized with the remaining enamel matrix residing within the enamel space. The expanding cysts derived from the enamel organ were formed in the periosteal connective tissue on the labial side. At the bottom of the tooth germs, the precursor cells of the epithelial root sheath were arranged regularly and the enamel organs were preserved to the same degree as those of normal rats. In the molar teeth of the affected rats an enamel matrix remained on the neck and crown of the erupted teeth; however, no abnormality was observed at the tooth root. Although an animal model of AI has been developed from mutants of the SHR-SP rat strain, the present cases represent another potential model of the disease because of the differences in the way the enamel matured and the odontogenic cyst formation in the incisors.