Cranial capacity/cranial base relationships and prediction of vault form: A canonical correlation analysis

Canonical correlation analysis was used to test an hypothesized morphological relationship between vault form and cranial capacity relative to length of the chondrocranium. Ninety-five adult male Czech skulls were measured for vault form expressed as length, width and height of the brain case; the chondrocranium was represented by nasion-basion and basion-opisthion lengths. In terms of explained variation, the first and most important dimension of covariation between vault and chondrocranial variables was size. The second most significant dimension of covariation expressed the hypothesized shape relationships—i.e., overall size being equal, the shorter the chondrocranial base relative to cranial capacity, the shorter and wider the vault. Furthermore, the competing hypothesis that vault form is determined by facial length proved untenable since facial length was predictive of vault shape only when measured as prosthion-basion, a measure that incorporates basal length. When corrected for basal length, facial length is unrelated to vault form. The results are consistent with the assumption that phylogenetic and microevolutionary trends toward brachycephaly in man stem from changes in the relationship between two components of skull growth, the chondrocranial base and the brain.     

Effects of annular cranial vault modification on the cranial base and face

Artificial modification of the cranial vault was practiced by a number of prehistoric and protohistoric populations, frequently during an infant's first year of life. We test the hypothesis that, in addition to its direct effects on the cranial vault, annular cranial vault modification has a significant indirect effect on cranial base and facial morphology. Two skeletal series from the Pacific Northwest Coast, which include both nonmodified and modified crania, were used: the Kwakiutl (62 nonmodified, 45 modified) and Nootka (28 nonmodified, 20 modified). Three-dimensional coordinates of 53 landmarks were obtained using a diagraph, and 36 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 and average modified crania, and the significance of the results were evaluated using a bootstrap test. Annular modification of the cranial vault produces significant effects on the morphology of the cranial base and face. Annular modification in the Kwakiutl resulted in restrictions of the cranial vault in the medial-lateral and superior-inferior dimensions and an increase in anterior-posterior growth. Similar dimensional changes are observed in the cranial base. The Kwakiutl face is increased anterior-posteriorly and reduced anterior-laterally to posterior-medially. Similar effects of modification are observed in the Nootka cranial vault and cranial base, though not in the face. These results demonstrate the developmental interdependence of the cranial vault, cranial base, and face. © 1993 Wiley-Liss, Inc.     

On the measurement of cranial thickness at nasion on cephalographs

Cranial bone thickness at nasion is difficult to measure by the conventional method of drawing a line at right angles to the tangent at nasion on the outer table. The difficulty arises from a lack of uniformity of the arc in this region. The proposed use of a constructed line, drawn at 30 degrees to the anterior projection of the Frankfort horizontal plane, provides an accurate, easily reproducible, and compatible alternative method of measurement.     

Effects of fronto-occipital artificial cranial vault modification on the cranial base and face.

Artificial reshaping of the cranial vault has been practiced by many human groups and provides a natural experiment in which the relationships of neurocranial, cranial base, and facial growth can be investigated. We test the hypothesis that fronto-occipital artificial reshaping of the neurocranial vault results in specific changes in the cranial base and face. Fronto-occipital reshaping results from the application of pads or a cradle board which constrains cranial vault growth, limiting growth between the frontal and occipital and allowing compensatory growth of the parietals in a mediolateral direction. Two skeletal series including both normal and artificially modified crania are analyzed, a prehistoric Peruvian Ancon sample (47 normal, 64 modified crania) and a Songish Indian sample from British Columbia (6 normal, 4 modified). Three-dimensional coordinates of 53 landmarks were measured with a diagraph and used to form 9 finite elements as a prelude to finite element scaling analysis. Finite element scaling was used to compare average normal and modified crania and the results were evaluated for statistical significance using a bootstrap test. Fronto-occipitally reshaped Ancon crania are significantly different from normal in the vault, cranial base, and face. The vault is compressed along an anterior-superior to posterior-inferior axis and expanded along a mediolateral axis in modified individuals. The cranial base is wider and shallower in the modified crania and the face is foreshortened and wider with the anterior orbital rim moving inferior and posterior towards the cranial base. The Songish crania display a different modification of the vault and face, indicating that important differences may exist in the morphological effects of fronto-occipital reshaping from one group to another.     

Determination of cranial capacity in fossil men

The cranial capacity of a skull of unknown origin can be determined by assuming that the product of the chief dimensions corresponds to a part of the endocranial volume. We start with formulas for present day man and determine their validity for fossil man. The equivalence differs in fossil men according to their taxonomic position. This method is useful even for damaged skulls, with porion and basion missing.     

Secondary brain tumors after cranial radiation therapy: A single-institution study

AimTo study the probability of developing secondary brain tumors after cranial radiotherapy.Background Patients treated with cranial radiotherapy are at risk for developing secondary brain tumors.Patients and methodsWe planned an institutional survey for secondary brain tumors in survivors after cranial irradiation and reviewed the 30-year duration data. Event analysis and cumulative proportion curves were performed to generally estimate the cumulative proportion of developing secondary brain tumors, cavernoma and meningioma at different periods of time.ResultsSecondary brain tumors occurred in 21% of cases: 10% were cavernomas, 6% were meningiomas, 3% were skull osteomas, and 1% were anaplastic astrocytoma. The cumulative proportion of developing secondary brain tumor was 6% at 10 years and 20% at 20 years, while the cumulative proportion for developing cavernomas and meningiomas was 16% and 7% at 20 years, respectively.ConclusionOur study shows that patients who received cranial irradiation were at risk of secondary brain tumors such as cavernomas and meningiomas. Thus, a meticulous follow-up of cancer survivors with history of cranial irradiation by an annual MRI scan is justifiable. This will help clinicians to detect secondary brain tumors early and make its management much easier.     

Artificial cranial deformation and the increased complexity of the lambdoid suture

Studies examining an association between artificial cranial deformation and the presence of wormian bones in the lambdoid suture have been inconclusive. Cranial deformation, however, does not seem to have a direct effect of increasing the sutural complexity of the pars lambdica of the lambdoid suture and also increasing the mean number of lambdoidal wormian bones, given their presence.     

Diachronic variation in cranial thickness of Near Eastern populations

Cephalometric radiographs were taken of 111 skulls of skeletal remains of populations living in Israel and Jordan during the last 12,000 years. From these radiographs, skull length and height, and cranial thickness were measured. For each sex and period, high correlations were found between cranial thickness at vertex, bregma, and lambda. Cranial thickness at nasion was correlated with sinus width but not sinus height. All measurements were correlated with skull length but not skull breadth. Using multivariate analysis, no significant differences in cranial thickness were found between the sexes. Significant diachronic trends were found in lambda and sinus width, and they were independent of variation in skull length.     

Effects of fronto-occipital cranial reshaping on mandibular form.

Cultural reshaping (artificial deformation or modification) of the neurocranial vault provides an artificially increased range of morphological variability within which the relationship between the growing neurocranium and face can be investigated. We analyze crania which have been fronto-occipitally compressed to ascertain possible morphological effects on the mandible. We collected measures of mandibular breadth, length, and height from 82 modified (N = 48) and unmodified (N = 34) crania from a Peruvian Ancon series. Angle classification was also scored in order to investigate whether or not occlusal relationships were affected by neurocranial reshaping. Only intercondylar distance (posterior mandibular breadth) exhibited significant differences between unmodified and modified groups, though this difference was relatively small compared with vault deformation. The modified crania had a higher frequency of normal occlusion (Class I) than the unmodified crania. Increased intercondylar breadth in modified skulls is due to a cascade of effects which begin with a direct effect of the fronto-occipital deforming device on neurocranial shape (increased neurocranial width). The increase in mandibular breadth may be a compensatory response to increased cranial base breadth and maintains articulation between the cranial base and mandible. The increased posterior breadth, coupled with a slight decrease in mandibular depth, may contribute to the change in occlusal relationships suggested for this sample.     

Distinct spatiotemporal roles of hedgehog signalling during chick and mouse cranial base and axial skeleton development

The cranial base exerts a supportive role for the brain and includes the occipital, sphenoid and ethmoid bones that arise from cartilaginous precursors in the early embryo. As the occipital bone and the posterior part of the sphenoid are mesoderm derivatives that arise in close proximity to the notochord and floor plate, it has been assumed that their development, like the axial skeleton, is dependent on Sonic hedgehog (Shh) and modulation of bone morphogenetic protein (Bmp) signalling. Here we examined the development of the cranial base in chick and mouse embryos to compare the molecular signals that are required for chondrogenic induction in the trunk and head. We found that Shh signalling is required but the molecular network controlling cranial base development is distinct from that in the trunk. In the absence of Shh, the presumptive cranial base did not undergo chondrogenic commitment as determined by the loss of Sox9 expression and there was a decrease in cell survival. In contrast, induction of the otic capsule occurred normally demonstrating that induction of the cranial base is uncoupled from formation of the sensory capsules. Lastly, we found that the early cranial mesoderm is refractory to Shh signalling, likely accounting for why development of the cranial base occurs after the axial skeleton. Our data reveal that cranial and axial skeletal induction is controlled by conserved, yet spatiotemporally distinct mechanisms that co-ordinate development of the cranial base with that of the cranial musculature and the pharyngeal arches.     

Postnatal growth of the cranial base in Macaca nemestrina.

Postnatal growth of the cranial base was longitudinally studied in 21 male and 11 female Macaca nemestrina. The basicranium of each animal was marked with tantulum implants in order that the tracings of each serial roentgenogram could be superimposed. Between the ages of 3.0 and 5.0 years the degree of sexual demorphism in both angular and linear dimensions increased. The cranial base flattened as a result of the upward and forward migration of nasion and the upward and backward relocation of basion. The movement of basion was primarily due to differential growth recorded at the spheno-occipital synchondrosis. Sexual difference in the relative growth of this synchondrosis resulted in a longer and somewhat flatter male cranial base. Male and female velocity curves showed accelerations that coincide with their estimated age for the onset of puberty.     

A method for whole protein isolation from human cranial bone

The presence of the dense hydroxyapatite matrix within human bone limits the applicability of conventional protocols for protein extraction. This has hindered the complete and accurate characterization of the human bone proteome thus far, leaving many bone-related disorders poorly understood. We sought to refine an existing method of protein extraction from mouse bone to extract whole proteins of varying molecular weights from human cranial bone. Whole protein was extracted from human cranial suture by mechanically processing samples using a method that limits protein degradation by minimizing heat introduction to proteins. The presence of whole protein was confirmed by western blotting. Mass spectrometry was used to sequence peptides and identify isolated proteins. The data have been deposited to the ProteomeXchange with identifier PXD003215. Extracted proteins were characterized as both intra- and extracellular and had molecular weights ranging from 9.4 to 629 kDa. High correlation scores among suture protein spectral counts support the reproducibility of the method. Ontology analytics revealed proteins of myriad functions including mediators of metabolic processes and cell organelles. These results demonstrate a reproducible method for isolation of whole protein from human cranial bone, representing a large range of molecular weights, origins and functions.     

Semaphorin signaling guides cranial neural crest cell migration in zebrafish

Cranial neural crest cells (NCCs) migrate into the pharyngeal arches in three primary streams separated by two cranial neural crest (NC)-free zones. Multiple tissues have been implicated in the guidance of cranial NCC migration; however, the signals provided by these tissues have remained elusive. We investigate the function of semaphorins (semas) and their receptors, neuropilins (nrps), in cranial NCC migration in zebrafish. We find that genes of the sema3F and sema3G class are expressed in the cranial NC-free zones, while nrp2a and nrp2b are expressed in the migrating NCCs. sema3F/3G expression is expanded homogeneously in the head periphery through which the cranial NCCs migrate in lzr/pbx4 mutants, in which the cranial NC streams are fused. Antisense morpholino knockdown of Sema3F/3G or Nrp2 suppresses the abnormal cranial NC phenotype of lzr/pbx4 mutants, demonstrating that aberrant Sema3F/3G-Nrp2 signaling is responsible for this phenotype and suggesting that repulsive Sema3F/3G-Npn2 signaling normally contributes to the guidance of migrating cranial NCCs. Furthermore, global over-expression of sema3Gb phenocopies the aberrant cranial NC phenotype of lzr/pbx4 mutants when endogenous Sema3 ligands are knocked down, consistent with a model in which the patterned expression of Sema3 ligands in the head periphery coordinates the migration of Nrp-expressing cranial NCCs.     

The development and distribution of the cranial neural crest in the rat embryo

Summary The head region of rat embryos was investigated by scanning electron microscopy after removal of the surface ectoderm with adhesive tape. Observations were made in embryos from 6-somite to 11-somite stages of development, in order to determine: (1) the sequence of emigration of neural crest cells from the different regions of the future brain; (2) the appearance of crest cells before, during, and after their conversion from an epithelial to a mesenchymal form; (3) the migration pathways.Emigration occurs first from the midbrain, and next from the rostral hindbrain; crest cells from these two regions migrate into the first visceral arch. Subsequently cells emigrate from the caudal hindbrain, but not in a rostrocaudal sequence. At the time of crest cell emigration, the neural fold morphology varies from a slightly convex, widely open plate (midbrain) to a closed tube (caudal hindbrain). Thus the timing of emigration is related neither to age (as reflected in rostrocaudal levels) nor to morphology of the neural epithelium.     

Integrin alpha5beta1 supports the migration of Xenopus cranial neural crest on fibronectin

During early embryonic development, cranial neural crest cells emerge from the developing mid- and hindbrain. While numerous studies have focused on integrin involvement in trunk neural crest cell migration, comparatively little is known about mechanisms of cranial neural crest cell migration. We show that fibronectin, but not laminin, vitronectin, or type I collagen can support cranial neural crest cell migration and segmentation in vitro. These behaviors require both the RGD and "synergy" sites located within the central cell-binding domain of fibronectin. While these two sites are sufficient for cranial neural crest cell migration, we find that the second Heparin-binding domain of fibronectin can provide additional support for cranial neural crest cell migration in vitro. Finally, using a function blocking monoclonal antibody, we show that cranial neural crest cell migration on fibronectin requires the integrin alpha5beta1.     

Signaling mechanisms controlling cranial placode neurogenesis and delamination

The neurogenic cranial placodes are a unique transient epithelial niche of neural progenitor cells that give rise to multiple derivatives of the peripheral nervous system, particularly, the sensory neurons. Placode neurogenesis occurs throughout an extended period of time with epithelial cells continually recruited as neural progenitor cells. Sensory neuron development in the trigeminal, epibranchial, otic, and olfactory placodes coincides with detachment of these neuroblasts from the encompassing epithelial sheet, leading to delamination and ingression into the mesenchyme where they continue to differentiate as neurons. Multiple signaling pathways are known to direct placodal development. This review defines the signaling pathways working at the finite spatiotemporal period when neuronal selection within the placodes occurs, and neuroblasts concomitantly delaminate from the epithelium. Examining neurogenesis and delamination after initial placodal patterning and specification has revealed a common trend throughout the neurogenic placodes, which suggests that both activated FGF and attenuated Notch signaling activities are required for neurogenesis and changes in epithelial cell adhesion leading to delamination. We also address the varying roles of other pathways such as the Wnt and BMP signaling families during sensory neurogenesis and neuroblast delamination in the differing placodes.     

Three-dimensional cranial surface reconstructions using high-resolution computed tomography

Until recently, there has been no satisfactory way for anthropologists to visualize intracranial morphology in more than two dimensions without actually "invading" the skull in some manner. Images provided by conventional x-ray and computed tomography (CT) scans are often abstract, flat, two-dimensional representations that fail to reveal three-dimensional relationships. We describe new computer-imaging techniques that reconstruct three-dimensional images from sequential series of narrowly collimated (1-2 mm), high-resolution CT scans of the skull. These computed images represent three-dimensional surface data and can be viewed from any direction. Depth information is encoded in gray scale. In addition, selected portions of the anatomy can be "removed", i.e., made transparent, to allow visualization of previously hidden intracranial morphology. Since the geometric data obtained with the CT scanner are precise, parameters such as linear distances, angles, areas, and volumes can be accurately (and instantaneously) generated. The power and versatility of these computer-imaging techniques are demonstrated by examining living subjects with major craniofacial dysmorphology (Treacher-Collins syndrome and unilateral coronal synostosis); an anthropoid osteological specimen (Gorilla); and a fossil mammal skull.     

Unusually low sexual dimorphism of endocranial capacity in a Zulu cranial series

The mean cranial capacities of 50 male and 50 female Zulu crania were found to be 1373.3 +/- 107.4 ml for males and 1251.2 +/- 101.1 ml for females (means +/- SD). The male value resembles that of other Negro groups, while the female value is somewhat higher than the value for Negro crania as a whole. The index of sexual dimorphism is 8.9%, which is low when compared with those of other Negroid series and other populations. The possible causes for this form of a low sexual dimorphism are as follows: A negative secular trend, with the assumption that the Zulu crania were larger than those of the reference populations of African Negroids before the start of the secular trend change. This would seem to be the most likely possibility, with some supporting evidence for both parts of the explanation. An absence of secular trend, with a demographic sampling aberration, in which large females and small males of the population are sampled. This possibility cannot be totally excluded. An absence of secular trend, with a genetic difference in sexual dimorphism for cranial capacity between the Zulu and the reference populations. While this possibility cannot be excluded, it would be the least preferable explanation.     

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.     

Myosin-X is critical for migratory ability of Xenopus cranial neural crest cells

The neural crest is a highly migratory cell population, unique to vertebrates, that forms much of the craniofacial skeleton and peripheral nervous system. In exploring the cell biological basis underlying this behavior, we have identified an unconventional myosin, myosin-X (Myo10) that is required for neural crest migration. Myo10 is highly expressed in both premigratory and migrating cranial neural crest (CNC) cells in Xenopus embryos. Disrupting Myo10 expression using antisense morpholino oligonucleotides leads to impaired neural crest migration and subsequent cartilage formation, but only a slight delay in induction. In vivo grafting experiments reveal that Myo10-depleted CNC cells migrate a shorter distance and fail to segregate into distinct migratory streams. Finally, in vitro cultures and cell dissociation-reaggregation assays suggest that Myo10 may be critical for cell protrusion and cell-cell adhesion. These results demonstrate an essential role for Myo10 in normal cranial neural crest migration and suggest a link to cell-cell interactions and formation of processes.