Analysis and visualization of growth-related and treatment-induced craniofacial changes

An analysis and visualization of craniofacial shape changes due to growth or orthodontic treatment is presented. The suggested method is based on an adapted Karhunen-Loève decomposition of time-discrete data based on landmarks in lateral X-rays of the skull. It allows for a reduction of the high-dimensional dynamic problem to a few spatial modes representing synchronous components of growth patterns with time-dependent mode coefficients. The growth-related shape changes as well as the orthodontic treatment effects are visualized by overdrawing the underlying shape changes. The results based on this technique give insight into the still controversially discussed question to which degree the craniofacial skeletal structures can be influenced by orthodontic appliances.     

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.     

Phenotypic evolution of human craniofacial morphology after admixture: a geometric morphometrics approach

An evolutionary, diachronic approach to the phenotypic craniofacial pattern arisen in a human population after high levels of admixture and gene flow was achieved by means of geometric morphometrics. Admixture has long been studied after molecular data. Nevertheless, few efforts have been made to explain the morphological outcome in human craniofacial samples. The Spanish-Amerindian contact can be considered a good scenario for such an analysis. Here we present a comparative analysis of craniofacial shape changes observed between two putative ancestor groups, Spanish and precontact Aztecs, and two diachronic admixed groups, corresponding to early and late colonial periods from the Mexico's Central Valley. Quantitative shape comparisons of Amerindian, Spanish, and admixed groups were used to test the expectations of quantitative genetics for admixture events. In its simplest form, this prediction states that an admixed group will present phenotypic values falling between those of both parental groups. Results show that, in general terms, although the human skull is a complex, integrated structure, the craniofacial morphology observed fits the theoretical expectations of quantitative genetics. Thus, it is predictive of population structure and history. In fact, results obtained after the craniofacial analysis are in accordance with previous molecular and historical interpretations, providing evidence that admixture is a main microevolutionary agent influencing modern Mexican gene pool. However, expectations are not straightforward when moderate shape changes are considered. Deviations detected at localized structures, such as the upper and lower face, highlight the evolution of a craniofacial pattern exclusively inherent to the admixed groups, indicating that quantitative characters might respond to admixture in a complicated, nondirectional way.     

山顶洞101号男性头骨的三维颅面复原

山顶洞101号头骨化石是东亚地区保存最为完整的化石之一,是探讨东亚地区现代人起源的重要研究材料。本文依据数据集中现生人的面部软组织平均分布,提出了计算机三维颅面复原方法,实现了101号头骨生前面貌的预测复原。主要包括三个步骤：首先使用CT完成了101号男性头骨和下颌骨仿制模型的三维重建。然后,利用计算机技术将现生人的面部软组织分布作为101号头骨的面部软组织分布,实现了颅面虚拟复原,并采用手工绘画技巧再现了复原面貌的形态特征。最后,提出了一种基于面部软组织分布和面貌统计形状模型的形态分析方法,实现了颅面复原结果的评估。山顶洞101号头骨的复原面貌具有头部较长、额头前倾、眉弓粗壮等特征,与101号头骨的几何形态基本一致。该技术再现了更新世晚期人类的脑颅及面部的形态特征,为古人类颅面复原的研究提供了技术支持和参考资料。     

Visualizing patterns of craniofacial shape variation in Homo sapiens

The geometric morphometric analysis of shape variation in complex biological structures such as the human skull poses a number of specific challenges: the registration of homologous morphologies, the treatment of bilateral symmetry, the graphical representation of form variability in three dimensions and the interpretation of the results in terms of differential growth processes. To visualize complex patterns of shape change, we propose an alternative to classical Cartesian deformation grids in the style of D'Arcy W. Thompson. Reference to the surface structures of the organism under investigation permits a comprehensive visual grasp of shape change and its tentative interpretation in terms of differential growth. The application of this method to the analysis of human craniofacial shape variation reveals distinct modes of growth and development of the neurocranial and viscerocranial regions of the skull. Our data further indicate that variations in the orientation of the viscerocranium relative to the neurocranium impinge on the shapes of the face and the cranial vault.     

Elastic properties of external cortical bone in the craniofacial skeleton of the rhesus monkey

Knowledge of elastic properties and of their variation in the cortical bone of the craniofacial skeleton is indispensable for creating accurate finite-element models to explore the biomechanics and adaptation of the skull in primates. In this study, we measured elastic properties of the external cortex of the rhesus monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight cylindrical cortical specimens were removed from each of six craniofacial skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal and transverse ultrasonic velocities were measured on each specimen to allow calculation of the elastic properties in three dimensions, according to equations derived from Newton's second law and Hooke's law. The axes of maximum stiffness were determined by fitting longitudinal velocities measured along the perimeter of each cortical specimen to a sinusoidal function. Results showed significant differences in elastic properties between different functional areas of the rhesus cranium, and that many sites have a consistent orientation of maximum stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull can be modeled as orthotropic in many regions, and as transversely isotropic in some regions, e.g., the supraorbital region. There are differences from human crania, suggesting that structural differences in skeletal form relate to differences in cortical material properties across species. These differences also suggest that we require more comparative data on elastic properties in primate craniofacial skeletons to explore effectively the functional significance of these differences, especially when these differences are elucidated through modeling approaches, such as finite-element modeling.     

Craniofacial form and function in Metriorhynchidae (Crocodylomorpha: Thalattosuchia): modelling phenotypic evolution with maximum-likelihood methods

Metriorhynchid crocodylomorphs were the only group of archosaurs to fully adapt to a pelagic lifestyle. During the Jurassic and Early Cretaceous, this group diversified into a variety of ecological and morphological types, from large super-predators with a broad short snout and serrated teeth to specialized piscivores/teuthophages with an elongate tubular snout and uncarinated teeth. Here, we use an integrated repertoire of geometric morphometric (form), biomechanical finite-element analysis (FEA; function) and phylogenetic data to examine the nature of craniofacial evolution in this clade. FEA stress values significantly correlate with morphometric values representing skull length and breadth, indicating that form and function are associated. Maximum-likelihood methods, which assess which of several models of evolution best explain the distribution of form and function data on a phylogenetic tree, show that the two major metriorhynchid subclades underwent different evolutionary modes. In geosaurines, both form and function are best explained as evolving under 'random' Brownian motion, whereas in metriorhynchines, the form metrics are best explained as evolving under stasis and the function metric as undergoing a directional change (towards most efficient low-stress piscivory). This suggests that the two subclades were under different selection pressures, and that metriorhynchines with similar skull shape were driven to become functionally divergent.     

Virtual Functional Morphology: Novel Approaches to the Study of Craniofacial Form and Function

Recent developments in simulating musculoskeletal functioning in the craniofacial complex using multibody dynamic analysis and finite elements analysis enable comprehensive virtual investigations into musculoskeletal form and function. Because the growth of the craniofacial skeleton is strongly influenced by mechanical functioning, these methods have potential in investigating the normal and abnormal development of the skull: loading history during development can be predicted and bony adaptations to these loads simulated. Thus these methods can be used to predict the impact of altered loading or modifications of skull form early in ontogeny on the subsequent development of structures. Combining functional models with geometric morphometric methods (GMM), which are principally concerned with the study of variations of form, offers the opportunity to examine variations in form during development and the covariations between form and factors such as functional performance. Such a combination of functional models and GMM can potentially be applied in many useful ways, for example: to build and modify functional models, to assess the outcomes of remodelling studies by comparing the results with morphological changes during ontogeny, and to compare the outcomes of finite element analyses within a multivariate framework. Studies using these tools can not only investigate the development of the skull but also the mechanical processes and thus to some degree, behaviours underlying the development of variation among extant and fossil skeletal elements. By bringing together these tools from quite different comparative traditions, a novel and potentially powerful framework for simulation and statistical biomechanical analyses of form and function emerges. This paper reviews these recent developments in the context of the evolutionary and functional influences on skull development.     

Finite element scaling analysis of human craniofacial growth

The study of form change is central to traditional cephalometric research. Unfortunately, traditional cephalometric studies operate within systems of measurement that are based on registration and orientation. Measurements produced in registered systems are insufficient for the craniofacial biologist who is interested in locating morphological differences between forms. In this article we apply a registration-free method called finite element scaling analysis in a study of the form change occurring during growth of the normal human craniofacial complex. The method provides form change data that can be summarized at various morphological levels. Twenty normal male individuals are used to analyze the form change that occurs from age 4 to ages 5, 7, 8, 9, 10, 12, 13, and 15 years. The magnitude and direction of growth expressed as shape and size change specific to craniofacial landmarks are presented. Although exceptions occur, our analysis shows that localized size change is, on the average, greater than localized shape change. The relation between size and shape change during growth shows allometry (shape change increasing during growth along with size change) but at a lesser magnitude and slower rate. We conclude that although shape change occurs throughout ontogeny, the magnitude and rate of shape change in relation to size change diminishes as age increases. This analysis represents new insights into the understanding of human craniofacial growth at various levels of morphological integration.     

Early Lens Ablation Causes Dramatic Long-Term Effects on the Shape of Bones in the Craniofacial Skeleton of Astyanax mexicanus

The Mexican tetra, Astyanax mexicanus, exists as two morphs of a single species, a sighted surface morph and a blind cavefish. In addition to eye regression, cavefish have an increased number of taste buds, maxillary teeth and have an altered craniofacial skeleton compared to the sighted morph. We investigated the effect the lens has on the development of the surrounding skeleton, by ablating the lens at different time points during ontogeny. This unique long-term study sheds light on how early embryonic manipulations on the eye can affect the shape of the adult skull more than a year later, and the developmental window during which time these effects occur. The effects of lens ablation were analyzed by whole-mount bone staining, immunohistochemisty and landmark based morphometric analyzes. Our results indicate that lens ablation has the greatest impact on the skeleton when it is ablated at one day post fertilisation (dpf) compared to at four dpf. Morphometric analyzes indicate that there is a statistically significant difference in the shape of the supraorbital bone and suborbital bones four through six. These bones expand into the eye orbit exhibiting plasticity in their shape. Interestingly, the number of caudal teeth on the lower jaw is also affected by lens ablation. In contrast, the shape of the calvariae, the length of the mandible, and the number of mandibular taste buds are unaltered by lens removal. We demonstrate the plasticity of some craniofacial elements and the stability of others in the skull. Furthermore, this study highlights interactions present between sensory systems during early development and sheds light on the cavefish phenotype.     

福建漳平奇和洞发现的新石器时代早期人类头骨

2011年在福建漳平奇和洞发现的距今1万年左右的新石器时代早期人类遗骸"奇和洞III号",是迄今在福建地区发现的最早、最完整的古人类头骨,为探讨华南更新世晚期向全新世过渡阶段人类的体质特征及现代人群的形成与分化提供了重要的研究材料。本文对这件头骨进行了研究,奇和洞III号为35岁左右的男性个体,牙齿龋病严重,推测当时人类的经济模式主要以农耕为主。通过与更新世晚期柳江、山顶洞101号及14组新石器时代人类头骨的比较,发现奇和洞III号头骨兼有更新世晚期人类及新石器南、北方居民的混合体质特征:奇和洞III号头骨长而脑量大,似更新世晚期人类;其高而狭窄的面部、宽阔而低矮的鼻部,呈现出不同于南、北方人群的特殊体质特征。主成分分析显示,奇和洞III号与对比的新石器时代各组在头骨的测量数据上没有表现为明显的南、北地区间差异,但在头骨的测量指数或形状上存在时代和地区间的不同。本文研究为新旧石器过渡阶段人类体质特征的变异提供了进一步证据。     

三维技术对安徽白鹭洲战国墓M566墓主容貌的复原

2011年安徽白鹭洲发现战国时期保存完整的楚国贵族墓葬,因墓主人头发和发簪保存完好、墓主身份显赫而备受关注。该头骨保存完整,具有亚洲蒙古人种的特征,根据骨骼的形态推测其为女性,年龄为35-39岁。为展现该地区战国贵族妇女的容貌、丰富该地区考古多样性提供研究材料。本文首先使用高分辨率CT对该个体的头骨及下颌骨进行了扫描和重建,然后采用基于偏最小二乘回归的颅面复原方法实现生前容貌基本形态的复原。最后,结合考古资料,利用三维模型处理软件对面貌复原模型及其发饰进行了三维建模和纹理贴图等处理,提高了颅面复原模型的真实感,生动形象地再现战国贵族女性面部的形态特征。     

Acute upregulation of hedgehog signaling in mice causes differential effects on cranial morphology

Hedgehog (HH) signaling, and particularly signaling by sonic hedgehog (SHH), is implicated in several essential activities during morphogenesis, and its misexpression causes a number of developmental disorders in humans. In particular, a reduced mitogenic response of cerebellar granule cell precursors to SHH signaling in a mouse model for Down syndrome (DS), Ts65Dn, is substantially responsible for reduced cerebellar size. A single treatment of newborn trisomic mice with an agonist of the SHH pathway (SAG) normalizes cerebellar morphology and restores some cognitive deficits, suggesting a possible therapeutic application of SAG for treating the cognitive impairments of DS. Although the beneficial effects on the cerebellum are compelling, inappropriate activation of the HH pathway causes anomalies elsewhere in the head, particularly in the formation and patterning of the craniofacial skeleton. To determine whether an acute treatment of SAG has an effect on craniofacial morphology, we quantitatively analyzed the cranial form of adult euploid and Ts65Dn mice that were injected with either SAG or vehicle at birth. We found significant deformation of adult craniofacial shape in some animals that had received SAG at birth. The most pronounced differences between the treated and untreated mice were in the midline structures of the facial skeleton. The SAG-driven craniofacial dysmorphogenesis was dose-dependent and possibly incompletely penetrant at lower concentrations. Our findings illustrate that activation of HH signaling, even with an acute postnatal stimulation, can lead to localized dysmorphology of the skull by generating modular shape changes in the facial skeleton. These observations have important implications for translating HH-agonist-based treatments for DS.KEY WORDS: Hedgehog signaling, Craniofacial shape, Down syndrome, Geometric morphometrics     

Use of a natural hybrid zone for genomewide association mapping of craniofacial traits in the house mouse

The identification of the genes involved in morphological variation in nature is still a major challenge. Here, we explore a new approach: we combine 178 samples from a natural hybrid zone between two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus), and high coverage of the genome (~ 145K SNPs) to identify loci underlying craniofacial shape variation. Due to the long history of recombination in the hybrid zone, high mapping resolution is anticipated. The combination of genomes from subspecies allows the mapping of both, variation within subspecies and inter‐subspecific differences, thereby increasing the overall amount of causal genetic variation that can be detected. Skull and mandible shape were measured using 3D landmarks and geometric morphometrics. Using principal component axes as phenotypes, and a linear mixed model accounting for genetic relatedness in the mapping populations, we identified nine genomic regions associated with skull shape and 10 with mandible shape. High mapping resolution (median size of significant regions = 148 kb) enabled identification of single or few candidate genes in most cases. Some of the genes act as regulators or modifiers of signalling pathways relevant for morphological development and bone formation, including several with known craniofacial phenotypes in mice and humans. The significant associations combined explain 13% and 7% of the skull and mandible shape variation, respectively. In addition, a positive correlation was found between chromosomal length and proportion of variation explained. Our results suggest a complex genetic architecture for shape traits and support a polygenic model.     

Les Attracteurs Inedits de l'hominisation

The recent discovery of a phenomenon of craniofacial growth, called craniofacial contraction, throws a new light on the process of hominization. The main interest of this discovery lies in a growth principle combining the different craniofacial units, that is to say, the neurocranium (neural skull), the chondrocranium (basal skull) and the splanchnocranium (visceral archs including the mandible). Until recent years, these different parts were considered as neighbouring element without any morphogenic or morphodynamic connection. But now, we know that the morphogenesis of the base of the skull governs that of the face. This basicranial morphogenesis is the occipital flexion. It generates morphogenic correlations with the face since embryogenesis. The ontogenic pathway of this phenomenon is the craniofacial contraction. It concerns embryonic dynamics connected with the spatial development of the embryonic neural system, the neural tube. These morphodynamics are common to each primate species, but they are differenciated by the amplitude of the embryonic contraction. We ask ourself the question: is hominization of the neurocephalic embryogenesis, that is the craniofacial contraction, plausible over a very long period, with gradual and chaotic evolutionary pathways, or, on the contrary, is the complexity of such an embryonic phenomenon, a limiting factor generating determined and predictible ontogenic thresholds? The study of extant and fossil primate skulls demonstrates that species are organized around 6 levels of embryonic contraction, which, starting from 60 millions years, evolve from the less to the most contracted skull. Among each ontogenic level, living and fossil species develop from the same embryonic system but between both levels, the embryos suddenly are reorganized. Therefore, I have defined an evolutive ontogenic unity, that is the fundamental ontogenesia. The cephalic pole has a fundamental ontogenesis, meaning that, beyond the diversities, we can see the same contraction in many living and extinct species. The ontogenic diversities are the result of the microevolution and are not predictible. In such a perspective, the ontogenic morphodynamics evolve with chaotic trajectories. But, between two embryonic levels, or two fundamental ontogeneses, evolutionary modalities are different. Eventually, from 60 millions years to XXth century, we observe the same phenomenon than during human ontogenesis; hominization of the cephalic pole is a craniofacial contraction. The evolutive pathway is stable, whatever the number of thresholds, the cranial shape changes but the ontogenic trajectory is preserved. This is a macroevolution because the embryonic system is reorganized. The logics of the phenomenon are an increasing dynamization, the human ontogenesis is the more unstable and the longer morphodynamics to stabilize the craniofacial contraction. To conclude, hominization is an iteration of an ontogenic process when embryos reach successive dynamic thresholds. The attractors are neither static, periodic, nor chaotic because the successive ontogenic trajectories are themselves in a stable evolutive trajectory, and the results with increasing contraction, complexified neocortical tissues and cephalocaudal reorganization are predictible. During hominization, irreversibility and innovations do not emerge with chaotic determinism, but with harmonic determinism in association with the correlations established between the embryonic tissues. When the system is destabilized, the embryonic systems do not forget the previous ontogenic pattern, on the contrary, they develop the pattern with new dynamical conditions. This sort of phenomenon is not described in the sciences of complexity. In the present case, we are in front of many millions years and the necessity to propose new concepts such as a new familly of attractors, namely the harmonic attractors.     

Epigenetic interactions and the structure of phenotypic variation in the cranium

Understanding the developmental and genetic basis for evolutionarily significant morphological variation in complex phenotypes such as the mammalian skull is a challenge because of the sheer complexity of the factors involved. We hypothesize that even in this complex system, the expression of phenotypic variation is structured by the interaction of a few key developmental processes. To test this hypothesis, we created a highly variable sample of crania using four mouse mutants and their wild-type controls from similar genetic backgrounds with developmental perturbations to particular cranial regions. Using geometric morphometric methods we compared patterns of size, shape, and integration in the sample within and between the basicranium, neurocranium, and face. The results highlight regular and predictable patterns of covariation among regions of the skull that presumably reflect the epigenetic influences of the genetic perturbations in the sample. Covariation between relative widths of adjoining regions is the most dominant factor, but there are other significant axes of covariation such as the relationship between neurocranial size and basicranial flexion. Although there are other sources of variation related to developmental perturbations not analyzed in this study, the patterns of covariation created by the epigenetic interactions evident in this sample may underlie larger scale evolutionary patterns in mammalian craniofacial form.     

Muscle‐induced loading as an important source of variation in craniofacial skeletal shape

The shape of the craniofacial skeleton is constantly changing through ontogeny and reflects a balance between developmental patterning and mechanical‐load‐induced remodeling. Muscles are a major contributor to producing the mechanical environment that is crucial for “normal” skull development. Here, we use an F₅ hybrid population of Lake Malawi cichlids to characterize the strength and types of associations between craniofacial bones and muscles. We focus on four bones/bone complexes, with different developmental origins, alongside four muscles with distinct functions. We used micro‐computed tomography to extract 3D information on bones and muscles. 3D geometric morphometrics and volumetric measurements were used to characterize bone and muscle shape, respectively. Linear regressions were performed to test for associations between bone shape and muscle volume. We identified three types of associations between muscles and bones: weak, strong direct (i.e., muscles insert directly onto bone), and strong indirect (i.e., bone is influenced by muscles without a direct connection). In addition, we show that although the shape of some bones is relatively robust to muscle‐induced mechanical stimulus, others appear to be highly sensitive to muscular input. Our results imply that the roles for muscular input on skeletal shape extend beyond specific points of origin or insertion and hold significant potential to influence broader patterns of craniofacial geometry. Thus, changes in the loading environment, either as a normal course of ontogeny or if an organism is exposed to a novel environment, may have pronounced effects on skeletal shape via near and far‐ranging effects of muscular loading.     

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.