Timing of ectocranial suture activity in Gorilla gorilla as related to cranial volume and dental eruption

Research has shown that Pan and Homo have similar ectocranial suture synostosis patterns and a similar suture ontogeny (relative timing of suture fusion during the species ontogeny). This ontogeny includes patency during and after neurocranial expansion with a delayed bony response associated with adaptation to biomechanical forces generated by mastication. Here we investigate these relationships for Gorilla by examining the association among ectocranial suture morphology, cranial volume (as a proxy for neurocranial expansion) and dental development (as a proxy for the length of time that it has been masticating hard foods and exerting such strains on the cranial vault) in a large sample of Gorilla gorilla skulls. Two-hundred and fifty-five Gorilla gorilla skulls were examined for ectocranial suture closure status, cranial volume and dental eruption. Regression models were calculated for cranial volumes by suture activity, and Kendall's tau (a non-parametric measure of association) was calculated for dental eruption status by suture activity. Results suggest that, as reported for Pan and Homo, neurocranial expansion precedes suture synostosis activity. Here, Gorilla was shown to have a strong relationship between dental development and suture activity (synostosis). These data are suggestive of suture fusion extending further into ontogeny than brain expansion, similar to Homo and Pan. This finding allows for the possibility that masticatory forces influence ectocranial suture morphology.     

Timing of Ectocranial Suture Activity in Pan troglodytes as Related to Cranial Volume and Dental Eruption

Research has shown that Pan and Homo have similar ectocranial suture synostosis patterns possibly because of their phylogenetic relationship. However, unlike human data, it is unclear if the ontogeny of suture activity for Pan exhibits a relationship with the expanding neurocranium or the masticatory apparatus. These relationships were assessed by examining the associations between ectocranial suture status and morphology and cranial volume (as a proxy for neurocranial expansion) and dental development (as an indicator of adulthood and proxy for masticatory influence) in a large sample of Pan troglodytes skulls. One hundred and fifty‐five P. troglodytes dry skulls were examined, and data were collected on ectocranial suture closure status, cranial volume, and dental eruption status. Regression models were calculated for suture status by cranial volumes, and Kendall's tau (a nonparametric measure of association) was calculated for suture status by dental eruption status. Results suggest that suture synostosis activity in P. troglodytes exhibits a period of stasis after neurocranial expansion cessation and does not have a strong relationship with brain development (r² ranged from 0.09 to 0.28), as similarly seen in Homo. Instead, suture synostosis has a stronger relationship with dental development (τ ranged from 0.59 to 0.72), where most osseous activity occurs after full adult dental eruption. This suggests that masticatory forces may influence both ectocranial suture morphology and synostosis more than brain expansion does in Pan, as also similarly noted in Homo. Anat Rec 293:1289–1296, 2010. © 2010 Wiley‐Liss, Inc.     

Trigonocephaly in rabbits with familial interfrontal suture synostosis: The multiple effects of premature single‐suture fusion

Previous studies from our laboratory have characterized the craniofacial morphology and growth patterns of an inbred strain of rabbits with autosomal dominant coronal suture synostosis. A number of rabbit perinates from this colony have been collected sporadically over a 5‐year period with premature interfrontal suture synostosis. The present study describes the very early onset of craniofacial dysmorphology of these rabbits and compares them to similar‐aged normal control rabbits. A total of 40 perinatal New Zealand White rabbits were used in the present study. Twenty‐one comprised the sample with interfrontal suture synostosis and ranged in age from 27 to 38 days postconception (term = 31 days) with a mean age of 33.53 days (±2.84 days). Nineteen rabbits served as age‐matched, normal controls (mean age = 33.05 days ±2.79 days). Lateral and dorsoventral radiographs were collected from each rabbit. The radiographs were traced, computer digitized, and 12 craniofacial measurements, angles, and indices were obtained. Mean measures were compared using an unpaired Student's t‐test. All synostosed rabbits were stillborn or died shortly after birth. Grossly, these rabbits exhibited extreme frontal bossing, trigonocephaly with sagittal keeling, and midfacial shortening. No somatic anomalies were noted. Radiographically, rabbits with interfrontal suture synostosis had significantly (P < 0.05) narrower bifrontal widths, shorter cranial vault lengths, kyphotic cranial base angles, and different cranial vault indices (shapes) compared to controls. Results reveal severe and early pathological and compensatory cranial vault changes associated with premature interfrontal suture synostosis in this rabbit model. The 100% mortality rate noted in this condition may be related to the inheritance of a lethal genetic mutation or to neural compression from reduced intracranial volume. Results are discussed in light of current pathogenic hypotheses for human infants with premature metopic suture synostosis. Anat Rec 260:238–251, 2000. © 2000 Wiley‐Liss, Inc.     

Ontogenetic Allometry and Cranial Shape Diversification Among Human Populations From South America

Modifications of ontogenetic allometries play an important role in patterning the shape differentiation among populations. This study evaluates the influence of size variation on craniofacial shape disparity among human populations from South America and assesses whether the morphological disparity observed at the interpopulation level resulted from a variable extension of the same ontogenetic allometry, or whether it arose as a result of divergences in the pattern of size‐related shape changes. The size and shape of 282 adult and subadult crania were described by geometric morphometric‐based techniques. Multivariate regressions were used to evaluate the influence of size on shape differentiation between and within populations, and phylogenetic comparative methods were used to take into account the shared evolutionary history among populations. The phylogenetic generalized least‐squares models showed that size accounts for a significant amount of shape variation among populations for the vault and face but not for the base, suggesting that the three modules did not exhibit a uniform response to changes in overall growth. The common slope test indicated that patterns of evolutionary and ontogenetic allometry for the vault and face were similar and characterized by a heightening of the face and a lengthening of the vault with increasing size. The conservation of the same pattern of shape changes with size suggests that differences in the extent of growth contributed to the interpopulation cranial shape variation and that certain directions of morphological change were favored by the trait covariation along ontogeny. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

Trigonocephaly in rabbits with familial interfrontal suture synostosis: the multiple effects of premature single-suture fusion

Previous studies from our laboratory have characterized the craniofacial morphology and growth patterns of an inbred strain of rabbits with autosomal dominant coronal suture synostosis. A number of rabbit perinates from this colony have been collected sporadically over a 5-year period with premature interfrontal suture synostosis. The present study describes the very early onset of craniofacial dysmorphology of these rabbits and compares them to similar-aged normal control rabbits. A total of 40 perinatal New Zealand White rabbits were used in the present study. Twenty-one comprised the sample with interfrontal suture synostosis and ranged in age from 27 to 38 days postconception (term = 31 days) with a mean age of 33.53 days (+/-2.84 days). Nineteen rabbits served as age-matched, normal controls (mean age = 33.05 days +/-2.79 days). Lateral and dorsoventral radiographs were collected from each rabbit. The radiographs were traced, computer digitized, and 12 craniofacial measurements, angles, and indices were obtained. Mean measures were compared using an unpaired Student's t-test. All synostosed rabbits were stillborn or died shortly after birth. Grossly, these rabbits exhibited extreme frontal bossing, trigonocephaly with sagittal keeling, and midfacial shortening. No somatic anomalies were noted. Radiographically, rabbits with interfrontal suture synostosis had significantly (P < 0.05) narrower bifrontal widths, shorter cranial vault lengths, kyphotic cranial base angles, and different cranial vault indices (shapes) compared to controls. Results reveal severe and early pathological and compensatory cranial vault changes associated with premature interfrontal suture synostosis in this rabbit model. The 100% mortality rate noted in this condition may be related to the inheritance of a lethal genetic mutation or to neural compression from reduced intracranial volume. Results are discussed in light of current pathogenic hypotheses for human infants with premature metopic suture synostosis.     

On the effect of cranial deformation in determining age from ectocranial suture closure

Available techniques for determining age from human cranial remains are limited. This study examines the efficacy of Meindl and Lovejoy's (1985) method of determining age based on ectocranial suture closure patterns as compared to a baseline of ages developed from a multifactorial approach employing various age determining factors from across the skull. What makes this study different is that the sample upon which this comparison is performed contains a large number of artificially deformed crania. Our hypothesis is that aging techniques that rely on suture closure patterns as markers are complicated by the results of artificial modification of the cranial vault. The study is conducted on adult, human crania from prehispanic archaeological sites in South America. Results demonstrate a significant difference between the two aging methods, more particularly when applied to deformed skulls. We conclude that when a skull is deformed age should be estimated utilizing multiple factors that exclude Meindl and Lovejoy's ectocranial suture aging technique.     

Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies

The mammalian skull vault is constructed principally from five bones: the paired frontals and parietals, and the unpaired interparietal. These bones abut at sutures, where most growth of the skull vault takes place. Sutural growth involves maintenance of a population of proliferating osteoprogenitor cells which differentiate into bone matrix-secreting osteoblasts. Sustained function of the sutures as growth centres is essential for continuous expansion of the skull vault to accommodate the growing brain. Craniosynostosis, the premature fusion of the cranial sutures, occurs in 1 in 2500 children and often presents challenging clinical problems. Until a dozen years ago, little was known about the causes of craniosynostosis but the discovery of mutations in the MSX2, FGFR1, FGFR2, FGFR3, TWIST1 and EFNB1 genes in both syndromic and non-syndromic cases has led to considerable insights into the aetiology, classification and developmental pathology of these disorders. Investigations of the biological roles of these genes in cranial development and growth have been carried out in normal and mutant mice, elucidating their individual and interdependent roles in normal sutures and in sutures undergoing synostosis. Mouse studies have also revealed a significant correspondence between the neural crest-mesoderm boundary in the early embryonic head and the position of cranial sutures, suggesting roles for tissue interaction in suture formation, including initiation of the signalling system that characterizes the functionally active suture.     

Masticatory HyperMuscularity is not Related to Reduced Cranial Volume in Myostatin‐Knockout Mice

It has been suggested recently that masticatory muscle size reduction in humans resulted in greater encephalization through decreased compressive forces on the cranial vault. Following this logic, if masticatory muscle size were increased, then a reduction in brain growth should also occur. This study was designed to test this hypothesis using a myostatin (GDF‐8) knockout mouse model. Myostatin is a negative regulator of skeletal muscle growth, and individuals lacking this gene show significant hypermuscularity. Sixty‐two [32 wild‐type (WT) and 30 GDF‐8 ‐/‐ knockout], 1, 28, 56, and 180‐day‐old CD‐1 mice were used. Body and masseter muscle weights were collected following dissection and standardized lateral and dorsoventral cephalographs were obtained. Cephalometric landmarks were identified on the radiographs and cranial volume was calculated. Mean differences were assessed using a two‐way ANOVA. KO mice had significantly greater body and masseter weights beginning at 28 days compared with WT controls. No significant differences in cranial volumes were noted between KO and WT. Muscle weight was not significantly correlated with cranial volume in 1, 28, or 180‐day‐old mice. Muscle weights exhibited a positive correlation with cranial volume at 56 days. Results demonstrate that masticatory hypermuscularity is not associated with reduced cranial volume. In contrast, there is abundant data demonstrating the opposite, brain growth determines cranial vault growth and masticatory apparatus only affects ectocranial morphology. The results presented here do not support the hypothesis that a reduction in masticatory musculature relaxed compressive forces on the cranial vault allowing for greater encephalization. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

Cranial sutures and bones: growth and fusion in relation to masticatory strain

Cranial bones and sutures are mechanically loaded during mastication. Their response to masticatory strain, however, is largely unknown, especially in the context of age change. Using strain gages, this study investigated masticatory strain in the posterior interfrontal and the anterior interparietal sutures and their adjacent bones in 3- and 7-month-old miniature swine (Sus scrofa). Double-fluorochrome labeling of these animals and an additional 5-month group was used to reveal suture and bone growth as well as features of suture morphology and fusion. With increasing age, the posterior interfrontal suture strain decreased in magnitude and changed in pattern from pure compression to both compression and tension, whereas the interparietal suture remained in tension and the magnitude increased unless the suture was fused. Morphologically, the posterior interfrontal suture was highly interdigitated at 3 months and then lost interdigitation ectocranially in older pigs, whereas the anterior interparietal suture remained butt-ended. Mineralization apposition rate (MAR) decreased with age in both sutures and was unrelated to strain. Bone mineralization was most vigorous on the ectocranial surface of the frontal and the parietal bones. Unlike the sutures, with age bone strain remained constant while bone MARs significantly increased and were correlated with bone thickness. Fusion had occurred in the interparietal suture of some pigs. In all cases fusion was ectocranial rather than endocranial. Fusion appeared to be associated with increased suture strain and enhanced bone growth on the ectocranial surface. Collectively, these results indicate that age is an important factor for strain and growth of the cranium. .     

Brain phenotypes in two FGFR2 mouse models for Apert syndrome

Apert syndrome (AS) is one of at least nine disorders considered members of the fibroblast growth factor receptor (FGFR) ‐1, ‐2, and ‐3–related craniosynostosis syndromes. Nearly 100% of individuals diagnosed with AS carry one of two neighboring mutations on Fgfr2. The cranial phenotype associated with these two mutations includes coronal suture synostosis, either unilateral (unicoronal synostosis) or bilateral (bicoronal synostosis). Brain dysmorphology associated with AS is thought to be secondary to cranial vault or base alterations, but the variation in brain phenotypes within Apert syndrome is unexplained. Here, we present novel three‐dimensional data on brain phenotypes of inbred mice at postnatal day 0 each carrying one of the two Fgfr2 mutations associated with AS. Our data suggest that the brain is primarily affected, rather than secondarily responding to skull dysmorphogenesis. Our hypothesis is that the skull and brain are both primarily affected in craniosynostosis and that shared phenogenetic developmental processes affect both tissues in craniosynostosis of Apert syndrome. Developmental Dynamics 239:987–997, 2010. © 2010 Wiley‐Liss, Inc.     

Relationship of brain and skull in pre- and postoperative sagittal synostosis

Models of vertebrate skull evolution stress the coordinated developmental relationship between the skull and the brain that it houses. This study investigates the relationship between altered skull morphology and brain morphology in premature fusion of the cranial sagittal suture (isolated sagittal synostosis; ISS), a condition associated with dysmorphology of both neurocranium and brain. Although the skull displays a more normal shape following reconstructive cranial vault surgery, effects of this surgery on the brain have not been investigated. Landmark coordinate data were collected from three-dimensional magnetic resonance imaging reconstructions of the brain in a sample of ISS patients and an age-matched unaffected cohort. These data were analysed using Euclidean distance matrix analysis (EDMA). Results show that the brain in ISS is dysmorphic preoperatively, displaying a posteriorly directed neural expansion that does not 'worsen' with growth. Postoperatively, the brain in ISS displays a more globular shape overall as compared with the preoperative morphology, but differs from normal in its subcortical morphology. These results show that the ISS brain is altered following neurocranial surgery, but does not more closely approximate that of unaffected individuals. This suggests that although the brain is affected by manipulation of the skull, it retains a growth pattern that is, at least in part, independent of the skull.     

Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis

Boundaries between cellular compartments often serve as signaling interfaces during embryogenesis. The coronal suture is a major growth center of the skull vault and develops at a boundary between cells derived from neural crest and mesodermal origin, forming the frontal and parietal bones, respectively. Premature fusion of these bones, termed coronal synostosis, is a common human developmental anomaly. Known causes of coronal synostosis include haploinsufficiency of TWIST1 and a gain of function mutation in MSX2. In Twist1(+/-) mice with coronal synostosis, we found that the frontal-parietal boundary is defective. Specifically, neural crest cells invade the undifferentiated mesoderm of the Twist1(+/-) mutant coronal suture. This boundary defect is accompanied by an expansion in Msx2 expression and reduction in ephrin-A4 distribution. Reduced dosage of Msx2 in the Twist1 mutant background restores the expression of ephrin-A4, rescues the suture boundary and inhibits craniosynostosis. Underlining the importance of ephrin-A4, we identified heterozygous mutations in the human orthologue, EFNA4, in three of 81 patients with non-syndromic coronal synostosis. This provides genetic evidence that Twist1, Msx2 and Efna4 function together in boundary formation and the pathogenesis of coronal synostosis.     

Changes in Biomechanical Strain and Morphology of Rat Calvarial Sutures and Bone After Tgf‐β3 Inhibition of Posterior Interfrontal Suture Fusion

Craniofacial sutures are bone growth fronts that respond and adapt to biomechanical environments. Little is known of the role sutures play in regulating the skull biomechanical environment during patency and fusion conditions, especially how delayed or premature suture fusion will impact skull biomechanics. Tgf‐β3 has been shown to prevent or delay suture fusion over the short term in rat skulls, yet the long‐term patency or its consequences in treated sutures is not known. It was therefore hypothesized that Tgf‐β3 had a long‐term impact to prevent suture fusion and thus alter the skull biomechanics. In this study, collagen gels containing 3 ng Tgf‐β3 were surgically placed superficial to the posterior interfrontal suture (IFS) and deep to the periosteum in postnatal day 9 (P9) rats. At P9, P24, and P70, biting forces and strains over left parietal bone, posterior IFS, and sagittal suture were measured with masticatory muscles bilaterally stimulated, after which the rats were sacrificed and suture patency analyzed histologically. Results demonstrated that Tgf‐β3 treated sutures showed less fusion over time than control groups, and strain patterns in the skulls of the Tgf‐β3‐treated group were different from that of the control group. Although bite force increased with age, no alterations in bite force were attributable to Tgf‐β3 treatment. These findings suggest that the continued presence of patent sutures can affect strain patterns, perhaps when higher bite forces are present as in adult animals. Anat Rec,, 2012. © 2012 Wiley Periodicals, Inc.     

CT-based description and phyletic evaluation of the archaic human calvarium from Ceprano, Italy

The discovery in 1994, of a fossilized human calvarium near Ceprano, Italy, dated about 800-900 thousand years before present, opened a new page for the study of human evolution in Europe. It extended the continental fossil record over the boundary between Early and Middle Pleistocene for the first time and revealed the cranial morphology of humans that where probably ancestral to both Neanderthals and modern Homo sapiens. A tomographic analysis of the Italian specimen is reported here in order to describe size and shape, vascular traces, and other features of the endocranium, as well as some relevant ectocranial traits (particularly of the frontal region). Our results show that the Ceprano calvarium displays plesiomorphies shared by early Homo taxa, involving a general archaic phenotype. At the same time, the presence of some derived features suggests a phylogenetic relationship with the populations referred to the subsequent polymorphic species H. heidelbergensis. The morphology of the supraorbital structures is different from the double-arched browridge of the African H. ergaster, while its superior shape shows similarities with African Middle Pleistocene specimens (Bodo, Kabwe). In contrast, the relationship between supraorbital torus and frontal squama points to an archaic pattern of the relationship between face and vault, associated to moderately narrow frontal lobes and limited development of the upper parietal areas. Despite a nonderived endocranial shape, the increase of cranial capacity (related to a general endocranial widening) and the probable absence of a clear occipital projection also suggest an evolutionary independence from the Asian H. erectus lineage. This analysis therefore supports the conclusion that the Ceprano calvarium represents the best available candidate for the ancestral phenotype of the cranial variation observed among Middle Pleistocene fossil samples in Africa and Europe. Nevertheless, a proper taxonomic interpretation of this crucial specimen remains puzzling.     

A geometric morphometric approach to the quantification of population variation in sub‐Saharan African crania

We report here on new data examining cranial variation in 18 modern human sub‐Saharan African populations. Previously, we investigated variation within southern Africa; we now extend our analyses to include a series of Central, East, and West African crania, to further knowledge of the relationships between, and variation and regional morphological patterning in, those populations. The sample comprises 377 male individuals; the three‐dimensional coordinates of 96 landmarks are analyzed using Procrustes‐based methods. Interpopulation variation is examined by calculating shape distances between groups, which are compared using resampling statistics and parametric tests. Phenotypic variance, as a proxy for genetic variance, is measured and compared across populations. Principal components and cluster analyses are employed to explore relationships between the populations. Shape differences are visualized using three‐dimensional rendered models. Observed disparity patterns imply a mix of differences and similarities across populations, with no apparent support for genetic bottlenecks, which is likely a consequence of migrations that may have influenced differences in cranial form; supporting data are found in recent molecular studies. The Pygmy sample had the most distinctive cranial morphology; characteristically small in size with marked prognathism. These features characterized, although less strongly, the neighboring Bateke, and are possibly related to similar selective pressures in conjunction with interbreeding. Small cranial size is also involved in the considerable distinctiveness of the San and Khoikhoi. The statistical procedures applied in this study afford a powerful and robust means of quantifying and visualizing the magnitude and pattern of cranial variation between sub‐Saharan African populations. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

Which cranial regions reflect molecular distances reliably in humans? Evidence from three‐dimensional morphology

Knowledge of the degree to which various subsets of morphological data reflect molecular relationships is crucial for studies attempting to estimate genetic relationships from patterns of morphological variation. This study assessed the phylogenetic utility of six different human cranial regions, plus the entire cranium. Three‐dimensional landmark data were collected for 83 landmarks from samples of skulls from 14 modern human populations. The data were subsequently divided into anatomical regions: basicranium, upper face, mandible, temporal bone, upper jaw, cranial vault, and a subset of points from around the entire cranium. Depictions of population molecular distances were calculated using published data on microsatellites for the same or closely related populations. Distances based on morphological variation of each of the anatomical regions were compared with molecular distances, and the correlations assessed. The morphology of the basicranium, temporal bone, upper face, and entire cranium demonstrated the highest correlations with molecular distances. The morphology of the mandible, upper jaw, and cranial vault, as measured here, were not significantly correlated with molecular distances. As the three‐dimensional morphology of the temporal bone, upper face, basicranium, and entire cranium appear to consistently reflect genetic relationships in humans, especially with more reliability than the cranial vault, it would be preferable to focus on these regions when attempting to determine the genetic relationships of human specimens with no molecular data. Am. J.Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.     

Balanced translocation in a patient with craniosynostosis disrupts the SOX6 gene and an evolutionarily conserved non-transcribed region

Craniosynostosis is a congenital developmental disorder involving premature fusion of cranial sutures, which results in an abnormal shape of the skull. Significant progress in understanding the molecular basis of this phenotype has been made for a small number of syndromic craniosynostosis forms. Nevertheless, in the majority of the ~100 craniosynostosis syndromes and in non‐syndromic craniosynostosis the underlying gene defects and pathomechanisms are unknown. Here we report on a male infant presenting at birth with brachycephaly, proptosis, midfacial hypoplasia, and low set ears. Three dimensional cranial computer tomography showed fusion of the lambdoid sutures and distal part of the sagittal suture with a gaping anterior fontanelle. Mutations in the genes for FGFR2 and FGFR3 were excluded. Standard chromosome analysis revealed a de novo balanced translocation t(9;11)(q33;p15). The breakpoint on chromosome 11p15 disrupts the SOX6 gene, known to be involved in skeletal growth and differentiation processes. SOX6 mutation screening of another 104 craniosynostosis patients revealed one missense mutation leading to the exchange of a highly conserved amino acid (p.D68N) in a single patient and his reportedly healthy mother. The breakpoint on chromosome 9 is located in a region without any known or predicted genes but, interestingly, disrupts patches of evolutionarily highly conserved non‐genic sequences and may thus led to dysregulation of flanking genes on chromosome 9 or 11 involved in skull vault development. The present case is one of the very rare reports of an apparently balanced translocation in a patient with syndromic craniosynostosis, and reveals novel candidate genes for craniosynostoses and cranial suture formation.     

Craniosynostosis: genes and mechanisms

Enlargement of the skull vault occurs by appositional growth at the fibrous joints between the bones, termed cranial sutures. Relatively little is known about the developmental biology of this process, but genetically determined disorders of premature cranial suture fusion (craniosynostosis) provide one route to the identification of some of the key molecules involved. Mutations of the MSX2, FGFR1, FGFR2, FGFR3 and TWIST genes yield new insights, both into normal and abnormal cranial suture biogenesis and into problems of broad interest, such as the conservation of molecular pathways in development, and mechanisms of mutation and dominance.      

Frequency variations of discrete cranial traits in major human populations. II. Hypostotic variations

Five discrete hypostotic cranial traits, tympanic dehiscence, ovale-spinosum confluence, metopism, transverse zygomatic suture vestige, and biasterionic suture, were investigated in 81 human population samples. Except for ovale-spinosum confluence, marked asymmetric occurrences of the bilateral traits were not detected in the majority of the samples. Significant intertrait association was observed mainly between the biasterionic suture and other sutural variations including accessory ossicles. The traits showing relatively consistent sex differences across diverse populations were tympanic dehiscence, which is predominant in females, and biasterionic suture in males. On a world scale, the 5 hypostotic cranial traits showed distinctive patterns of geographical variation. Different clinal variations within and between macrogeographical areas such as western and eastern parts of the Old World were found for the frequencies of the traits. The Ainu may be the most distinct outlier in the eastern Asian region on the basis of the incidence of the traits, especially the transverse zygomatic suture vestige. The interregional variation without reasonable adaptive value and nonadaptive shift of the possible outliers presented in this study suggest that the genetic background for the occurrence of these traits cannot be excluded completely.     

Cell adhesion molecule cadherin‐6 function in zebrafish cranial and lateral line ganglia development

Cadherins regulate the vertebrate nervous system development. We previously showed that cadherin‐6 message (cdh6) was strongly expressed in the majority of the embryonic zebrafish cranial and lateral line ganglia during their development. Here, we present evidence that cdh6 has specific functions during cranial and lateral line ganglia and nerve development. We analyzed the consequences of cdh6 loss‐of‐function on cranial ganglion and nerve differentiation in zebrafish embryos. Embryos injected with zebrafish cdh6 specific antisense morpholino oligonucleotides (MOs, which suppress gene expression during development; cdh6 morphant embryos) displayed a specific phenotype, including (i) altered shape and reduced development of a subset of the cranial and lateral line ganglia (e.g., the statoacoustic ganglion and vagal ganglion) and (ii) cranial nerves were abnormally formed. These data illustrate an important role for cdh6 in the formation of cranial ganglia and their nerves. Developmental Dynamics 240:1716–1726, 2011. © 2011 Wiley‐Liss, Inc.