Shape of the craniofacial complex in 45,X females: cephalometric study

The shape of the craniofacial complex was analysed cephalometrically in sixty-four adult 45,X females (Turner syndrome) using lateral skull radiographs, and the subjects were compared with first-degree female relatives and control females. The results showed that 45,X females have marked changes in relatively few craniofacial areas compared to the controls. Most of the changes are located in the cranial base, so that the face is retrognathic. The mandible is short, whereas the maxilla is of normal length. The results support the view that the morphology of the cranial base is markedly affected in 45,X females, whereas most other craniofacial changes could be considered secondary to the cranial base abnormality. It is suggested that retarded cartilage growth may be a factor leading to the present findings.     

Growth of cranial synchondroses and sutures requires polycystin-1

In vertebrates, coordinated embryonic and postnatal growth of the craniofacial bones and the skull base is essential during the expansion of the rostrum and the brain. Identification of molecules that regulate skull growth is important for understanding the nature of craniofacial defects and for development of non-invasive biologically based diagnostics and therapies.Here we report on spatially restricted growth defects at the skull base and in craniofacial sutures of mice deficient for polycystin-1 (Pkd1). Mutant animals reveal a premature closure of both presphenoid and sphenooccipital synchondroses at the cranial base. Furthermore, knockout mice lacking Pkd1 in neural crest cells are characterized by impaired postnatal growth at the osteogenic fronts in craniofacial sutures that are subjected to tensile forces. Our data suggest that polycystin-1 is required for proliferation of subpopulations of cranial osteochondroprogenitor cells of both mesodermal and neural crest origin during skull growth. However, the Erk1/2 signalling pathway is up-regulated in the Pkd1-deficient skeletal tissue, similarly to that previously reported for polycystic kidney.     

Skull base expansion: craniofacial effects

In order to determine what effect the anterior cranial base has on the developing craniofacial skeleton, mechanical expansion of the growth of one segment of the anterior cranial base was performed. New Zealand white rabbits were used for this study. A sham-treated group (n = 16) underwent implantation of dental amalgam markers to either side of the frontonasal, coronal, and lambdoid sutures at 9 days of age to serve as markers of vault growth. The experimental group (n = 7) underwent the same marker placement at 9 days of age, but, in addition, at 30 days of age these animals underwent placement of a mechanical spring, unilaterally, at the frontosphenoid suture. A second control group (n = 8) underwent the same exposure of the frontosphenoid suture, but the spring was laid only on the surface of the bone. All animals were followed by radiographic cephalometry at 9, 30, 60, and 90 days of age. The experimental group demonstrated statistically significant expansion of the cranial base and ipsilateral coronal suture. The midface skeletal dimensions were unchanged by spring distraction of the cranial base. These findings indicate that cranial base sutural growth can be manipulated mechanically and that growth changes can be attained secondarily in the cranial vault skeleton.     

The Developmental Basis of Quantitative Craniofacial Variation in Humans and Mice

The human skull is a complex and highly integrated structure that has long held the fascination of anthropologists and evolutionary biologists. Recent studies of the genetics of craniofacial variation reveal a very complex and multifactorial picture. These findings contrast with older ideas that posit much simpler developmental bases for variation in cranial morphology such as the growth of the brain or the growth of the chondrocranium relative to the dermatocranium. Such processes have been shown to have major effects on cranial morphology in mice. It is not known, however, whether they are relevant to explaining normal phenotypic variation in humans. To answer this question, we obtained vectors of shape change from mutant mouse models in which the developmental basis for the craniofacial phenotype is known to varying degrees, and compared these to a homologous dataset constructed from human crania obtained from a single population with a known genealogy. Our results show that the shape vectors associated with perturbations to chondrocranial growth, brain growth, and body size in mice do largely correspond to axes of covariation in humans. This finding supports the view that the developmental basis for craniofacial variation funnels down to a relatively small number of key developmental processes that are similar across mice and humans. Understanding these processes and how they influence craniofacial shape provides fundamental insights into the developmental basis for evolutionary change in the human skull as well as the developmental-genetic basis for normal phenotypic variation in craniofacial form.     

The ontogeny of cranial base angulation in humans and chimpanzees and its implications for reconstructing pharyngeal dimensions

This paper examines differences in the processes by which the cranial base flexes in humans and extends in chimpanzees. In addition, we test the extent to which one can use comparisons of cranial base angles in humans and non-human primates to predict vocal tract dimensions. Four internal cranial base angles and one external cranial base angle were measured in a longitudinal sample of Homo sapiens and a cross-sectional sample of Pan troglodytes. These data show that the processes of cranial base angulation differ substantially in these species. While the human cranial base flexes postnatally in a rapid growth trajectory that is complete by two years, the cranial base in P. troglodytes extends postnatally in a more prolonged skeletal growth trajectory. These comparisons also demonstrate that the rate of cranial base angulation is comparable for different measures, but that angles which incorporate different anterior cranial base measurements correlate poorly. We also examined ontogenetic relationships between internal and external cranial base angles and vocal tract growth in humans to test the hypothesis that cranial base angulation influences pharyngeal dimensions and can, therefore, be used to estimate vocal tract proportions in fossil hominids. Our results indicate that internal and external cranial base angles are independent of the horizontal and vertical dimensions of the vocal tract. Instead, a combination of mandibular and palatal landmarks can be used to predict dimensions of the vocal tract in H. sapiens. The developmental contrasts in cranial base angulation between humans and non-human primates may have important implications for testing hypotheses about the relationship between cranial base flexion and other craniofacial dimensions in hominid evolution.     

BMP4 promotes chondrocyte proliferation and hypertrophy in the endochondral cranial base

Defects in the growth and development of the endochondral bones that comprise the cranial base contribute to several craniofacial dysmorphic syndromes. Since Bone Morphogenetic Protein (BMP) signaling regulates chondrocyte differentiation and endochondral ossification in developing long bones, we have tested the hypothesis that BMP signaling also participates in regulating development of the cranial base. During in vivo developmental progression of the cranial base in mice, a burst of skeletal growth and chondrocyte maturation was identified in the perinatal period. Using a novel serum-free organ culture system, cranial base structures were cultured as explants in the presence of BMP4 or noggin, and analyzed for morphological and molecular changes. Growth of perinatal cranial base explants was inhibited by treatment with noggin, a BMP inhibitor. Exogenous BMP4 promoted cartilage growth, matrix deposition and chondrocyte proliferation in a dose dependent manner. Correspondingly, expression level of the cartilage markers Sox9 and collagen type II were also increased. Alkaline phosphatase and collagen type X expression were up-regulated and expressed in ectopic hypertrophic chondrocytes after treatment of the cultures with 100 ng/ml BMP4 for seven days. This increase in chondrocyte hypertrophy was accompanied by increased indian hedgehog (Ihh) and parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor (PPR) expression, but not increased PTHrP expression. We conclude that endogenous BMPs are required to maintain cartilage growth, and exogenous BMP4 can enhance cartilage maturation and induce ectopic chondrocyte hypertrophy in the cranial base. Therefore, appropriate levels of BMP signaling are important for normal cranial base development.     

Growth changes in internal and craniofacial flexion measurements.

Growth changes in both internal and craniofacial flexion angles are presented for Pan troglodytes, Gorilla gorilla, and modern humans. The internal flexion angle (IFA) was measured from lateral radiographs, and the craniofacial flexion angle (CFA) was calculated from coordinate data. Stage of dental development is used as a baseline for examination of growth changes and nonparametric correlations between flexion angles and dental development stage are tested for significance. In Gorilla, the IFA increases during growth. The IFA is relatively stable in Pan and modern humans. Pan and Gorilla display an increase in the CFA. However, this angle decreases during growth in modern humans. Flexion angles were derived from coordinate data collected for several early hominid crania. Measurements for two robust australopithecine crania indicate strong internal flexion. It has been suggested that cerebellar expansion in this group may relate to derived features of the posterior cranial base. In general, australopithecine crania exhibit craniofacial flexion intermediate between great apes and modern humans. The "archaic" Homo sapiens specimen from Kabwe is most similar to modern humans.     

Implantation of cranial base metallic markers in nonhuman primates.

Cranial base metallic markers are useful in growth and developmental research on the nonhuman primate model. Metallic implants aid in superimposing serial cephalometric roentgenograms in the study of craniofacial changes. They also enable measurement of linear and angular changes in the cranial base. The design of a special implant gun is described in detail. A suggested technique for placement of tantalum markers in the cranial base of nonhuman primates is discussed.     

Testing hypotheses about tinkering in the fossil record: the case of the human skull

Efforts to test hypotheses about small-scale shifts in development (tinkering) that can only be observed in the fossil record pose many challenges. Here we use the origin of modern human craniofacial form to explore a series of analytical steps with which to propose and test evolutionary developmental hypotheses about the basic modules of evolutionary change. Using factor and geometric morphometric analyses of craniofacial variation in modern humans, fossil hominids, and chimpanzee crania, we identify several key shifts in integration (defined as patterns of covariation that result from interactions between components of a system) among units of the cranium that underlie the unique shape of the modern human cranium. The results indicate that facial retraction in modern humans is largely a product of three derived changes: a relatively longer anterior cranial base, a more flexed cranial base angle, and a relatively shorter upper face. By applying the Atchley-Hall model of morphogenesis, we show that these shifts are most likely the result of changes in epigenetic interactions between the cranial base and both the brain and the face. Changes in the size of the skeletal precursors to these regions may also have played some role. This kind of phenotype-to-genotype approach is a useful and important complement to more standard genotype-to-phenotype approaches, and may help to identify candidate genes involved in the origin of modern human craniofacial form.     

Hawaiian craniofacial morphometrics: Average Mokapuan skull,artificial cranial deformation,and the “rocker” mandible

Craniofacial morphology and cultural cranial deformation were analyzed by the computer morphometric system in 79 adult Hawaiian skulls from Mokapu, Oahu. The average Hawaiian male was large, but similar in shape to the female. Both were larger than the present Caucasian, showed a greater dental protrusion, and possessed a larger ANB angle, flatter cranial base, and larger facial heights. Correlations in Hawaiian craniofacial structure were found between an increasing mandibular plane angle and (1) shorter posterior facial height, (2) larger gonial angle, (3) larger cranial base angle, and (4) smaller SNA and SNB angles. Of the 79 skulls studied, 8. 9% were found to have severe head molding or intentional cranial deformation. Significant statistical differences between the molded group and the nonmolded group are, in decreasing significance: (1) larger upper face height, (2) smaller glabella to occiput distance, and (3) increased lower face height with deformation. The morphometric differences were readily seen by graphic comparison between groups. It is postulated that external forces to the neurocranium result in redirection of the growth vectors in the neurocranial functional matrix, including the cranial base, and secondarily, to the orofacial functional matrix. There is a possibility that the cranial deformation is a retention of the normal birth molding changes. The Polynesian “rocker jaw” was found in 81% to 95% of this populace. This mandibular form occurs only with attainment of adult stature and craniofacial form. This data agrees with the hypothesis that mandibular form is modified by the physical forces present and their direction in the orofacial functional matrix.     

Cranial base angulation and prognathism related to cranial and general skeletal maturation in human fetuses.

The purpose of the present study was to describe normal midsagittal craniofacial morphology in second trimester human fetuses. Measurements of the cranial base angle and the prognathism of the maxilla and the mandible were performed on radiographs of cranial midsagittal tissue blocks of 52 fetuses with a gestational age from 13 to 27 weeks. Special procedures were developed for the definitions of the nasion and sella reference points on the radiographs in the early stages of fetal development. Mean data were reported for stages of crown rump length (CRL) and maturation of the fetal cranial base (MSS), usable as reference in assessment of pathological fetal crania in reports and autopsy procedures. Regression equations were determined for the regression of the angular values on CRL, MSS, and general skeletal maturation (TNO). The cranial base angle was found to decrease significantly, and the angles of prognathism to increase significantly with increasing CRL, TNO, and MSS values. It was suggested that these simultaneous and similar changes in the three angles could be accounted for by the upwards movement of the sella point produced by a cranial displacement of the pituitary fossa caused by local cartilagenous growth and bony remodelling during the period of study. The study thus reflects the influence of cranial skeletal maturation on the early development in shape of the craniofacial complex.     

Asymmetric vault modification in Hopi crania

Cradleboarding was practiced by numerous prehistoric and historic populations, including the Hopi. In this group, one result of cra-dleboarding was bilateral or asymmetric flattening of the posterior occipital. We test whether cradleboarding had significant effects on the morphology of the cranial vault, cranial base, and face. Additionally, we examine associations between direction of flattening and asymmetric craniofacial growth. A skeletal sample of Hopi from the Old Walpi site includes both nonmodified (N = 43) and modified individuals (N = 39). Three-dimensional coordinates of 53 landmarks were obtained using a diagraph. Thirty-six landmarks were used to define nine finite elements in the cranial vault, cranial base, and face. Finite element scaling was used to compare average nonmodified individuals, with averages of bilaterally, right, and left modified individuals. The significance of variation among “treatment” groups was evaluated using a bootstrap test. Pearson product-moment correlations test the association of asymmetry with direction of modification. Hopi cradleboarding has a significant effect on growth of the cranial vault, but does not affect morphology of the cranial base or face. Bilateral flattening of the cranial vault leads to decreased length and increased width of the cranial vault. Flattening of the right or left cranial vault results in ipsilaterally decreased length and width coupled with a corresponding increased length and width on the contralateral side of the cranial vault. There is a significant correlation of size asymmetry with direction of modification in the cranial vault, but not with size or shape change in the cranial base or face. © 1995 Wiley-Liss, Inc.     

Expression of Cre recombinase in chondrocytes causes abnormal craniofacial and skeletal development

The cranial base synchondroses are growth centers that drive cranial and upper facial growth. The intersphenoid synchondrosis (ISS) and the spheno-occipital synchondrosis (SOS) are two major synchondroses located in the middle of the cranial base and are maintained at early developmental stages to sustain cranial base elongation. In this study, we report unexpected premature ossification of ISS and SOS when Cre recombinase is activated in a chondrocyte-specific manner. We used a Cre transgenic line expressing Aggrecan enhancer-driven, Tetracycline-inducible Cre (ATC), of which expression is controlled by a Col2a1 promoter. Neonatal doxycycline injection or doxycycline diet fed to breeders was used to activate Cre recombinase. The premature ossification of ISS and/or SOS led to a reduction in cranial base length and subsequently a dome-shaped skull. Furthermore, the mice carrying either heterozygous or homozygous conditional deletion of Tsc1 or Fip200 using ATC mice developed similar craniofacial abnormalities, indicating that Cre activity itself but not conditional deletion of Tsc1 or Fip200 gene, is the major contributor of this phenotype. In contrast, the Col2a1-Cre mice carrying Cre expression in both perichondrium and chondrocytes and the mice carrying the conditional deletion of Tsc1 or Fip200 using Col2a1-Cre did not manifest the same skull abnormalities. In addition to the defective craniofacial bone development, our data also showed that the Cre activation in chondrocytes significantly compromised bone acquisition in femur. Our data calls for the consideration of the potential in vivo adverse effects caused by Cre expression in chondrocytes and reinforcement of the importance of including Cre-containing controls to facilitate accurate phenotype interpretation in transgenic research.

     

Craniofacial suture stenosis: morphologic effects

Craniofacial anomalies, such as Apert's and Crouzon's syndromes, are presumed to be related to premature growth arrest of cranial base growth sites. However, premature growth arrest at cranial vault sutures in animals appears to play a causative role in the development of cranial deformities characteristic of single-suture, or simple, craniosynostosis in humans. To study the possible causative role of cranial vault and other (interface) suture stenoses on the development of craniofacial deformity, a vault suture and an interface suture between the cranial vault and facial skeleton were simultaneously immobilized. Thirty-one New Zealand White rabbits at 9 days of age underwent implantation of dental amalgam growth markers adjacent to cranial vault and facial sutures. In the experimental group (n = 15), methylcyanoacrylate adhesive was applied over the coronal (vault) and frontonasal (interface suture between vault and facial skeleton) sutures to immobilize them. The remaining 16 animals served as sham-treated controls. All animals underwent serial radiographic cephalometry to document growth effects in the cranial vault, cranial base, and facial skeleton. Application of adhesive resulted in statistically significant (p less than 0.05) reduction in growth at the coronal and frontonasal sutures. This was accompanied by an overall significant reduction in neurocranial vault length during the first 30 days of development.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of the craniofacial morphology in 2-month-old unoperated infants with unilateral complete cleft lip and palate, and unilateral incomplete cleft lip.

This paper reports a cephalometric analysis of the craniofacial morphology in infants with unoperated unilateral complete cleft lip and palate (UCCLP) and unoperated unilateral incomplete cleft lip (UICL). The purpose of the study was to determine the nature and extent of the craniofacial deviations in UCCLP as compared to the morphology in UICL, which has previously been shown to be close to normal. The samples comprised 82 infants with UCCLP (58 males and 24 females) and 75 with UICL (48 males and 27 females). The mean age was about 2 months in both groups. The cephalometric analysis of craniofacial morphology included the lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. The most pronounced deviations in the UCCLP group were observed in the maxillary complex and the mandible. The most striking findings were: markedly increased width of the maxilla, a short mandible, and bimaxillary retrognathia except for the premaxillary area, which was relatively protruding and asymmetric. The study did not support the hypothesis previously suggested in the literature that cleft lip and palate is a craniofacial anomaly as size and shape of the calvaria and cranial base were found to be normal. The etiology of cleft lip and palate is still incompletely understood. Based on the present study, we suggest that facial type may be a liability factor that could represent a developmental threshold increasing the probability of cleft lip and palate.     

Cephalometric analysis of the craniofacial region of the northern Foxe Basin Eskimo

Past investigations of the Eskimo have indicated that there are marked morphological differences in the craniofacial skeleton of this relatively isolated ethnic group compared to other ethnic and racial groups. This study, using cephalometric radiography, attempted to characterize the craniofacial phenotype of the Eskimo living in the northern Foxe Basin, Northwest Territories, Canada. Age changes were examined on a cross-sectional basis with comparisons being made with a Winnipeg Caucasian group. This investigation indicates that the Igloolik Eskimo has a phenotype, established early in life, and is distinct from the Winnipeg group. The overall size of the Eskimo craniofacial complex was significantly larger at three years of age and remained larger through the ages studied. Development of the craniofacial region, however, was fairly similar in rate and direction for both populations. The greatest differences between the Eskimo and Caucasian groups were found in the linear measurements assessing cranial width, facial width, mandibular length, facial height, protrusion of the incisors, chin point development, and nasal morphology. Differences between the two groups in the morphological relationships of the component structures include the angular relationships of the maxilla and nasal bones to the anterior cranial base, the gonial angle of the mandible, and the angle of facial convexity.     

Assessing cranial plasticity in humans: The impact of artificial deformation on masticatory and basicranial structures

Artificial cranial deformations (ACD) are a widespread cultural practice found in numerous historical and prehistoric contexts. Their study can yield valuable insight into craniofacial growth, specifically into the interactions between neurocranial and basicranial modules. This study seeks to reinvestigate the presumed effect of ACD on basicranial and masticatory elements by applying a 3D geometric morphometric approach to CT scans. A total of 51 French and Bolivian skulls, representing anteroposterior and circumferential deformations and including undeformed individuals, were scanned, and 3D landmarks were submitted to between-group principal components analysis and two-block partial least-squares analysis. Our results illustrate changes in basicranial shape and in cranial base angles induced by ACD, as well as in masticatory geometry, namely in the relative position of the mandibular fossae. Furthermore, our findings highlight differential effects of the various deformation types, which suggest that patterns of covariation between modified vaults and their associated basicrania are more complex than previously assumed, thereby stressing the degree of plasticity in human craniofacial growth.     

Postnatal Cranial Development in Papionin Primates: An Alternative Model for Hominin Evolutionary Development

The evolution of hominin growth and life history has long been a subject of intensive research, but it is only recently that paleoanthropologists have considered the ontogenetic basis of human morphological evolution. To date, most human EvoDevo studies have focused on developmental patterns in extant African apes and humans. However, the Old World monkey tribe Papionini, a diverse clade whose members resemble hominins in their ecology and population structure, has been proposed as an alternative model for human craniofacial evolution. This paper reviews prior studies of papionin development and socioecology and presents new analyses of juvenile shape variation and ontogeny to address fundamental questions concerning primate cranial development, including: (1) When are cranial shape differences between species established? (2) How do epigenetic influences modulate early-arising pattern differences? (3) How much do postnatal developmental trajectories vary? (4) What is the impact of developmental variation on adult cranial shape? and, (5) What role do environmental factors play in establishing adult cranial form? Results of this inquiry suggest that species differences in cranial morphology arise during prenatal or earliest postnatal development. This is true even for late-arising features that develop under the influence of epigenetic factors such as mechanical loading. Papionins largely retain a shared, ancestral pattern of ontogenetic shape change, but large size and sexual dimorphism are associated with divergent developmental trajectories, suggesting differences in cranial integration. Developmental simulation studies indicate that postnatal ontogenetic variation has a limited influence on adult cranial morphology, leaving early morphogenesis as the primary determinant of cranial shape. The ability of social factors to influence craniofacial development in Mandrillus suggests a possible role for phentotypic plasticity in the diversification of primate cranial form. The implications of these findings for taxonomic attribution of juvenile fossils, the developmental basis of early hominin characters, and hominin cranial diversity are discussed.