Prenatal development of skull and brain in a mouse model of growth restriction

Patterns of covariation result from the over-lapping effect of several developmental processes. By perturbing certain specific developmental processes, ex-perimental studies contribute to a better understanding of their particular effects on the generation of phenotype. The aim of this work was to analyze the interactions among morphological traits of the skull and the brain during late prenatal life (18.5 days postconception) in mice exposed to maternal protein undernutrition. Images from the skull and brain were obtained through micro-computed tomography and 3D landmark coordinates were digitized in order to quantify shape and size of both structures with geometric morphometric techniques. The results highlight a systemic effect of protein restriction on the size of the skull and the brain, which were both significantly reduced in the under-nourished group compared to control group. Skull shape is partially explained by brain size, and patterns of shape variation were only partially coincident with previous re-ports for other ontogenetic stages, suggesting that allomet-ric trajectories across pre- and postnatal ages change their directions. Within the skull, neurocranial and facial shape traits covaried strongly, while subtle covariation was found between the shape of the skull and the brain. These find-ings are in line with former studies in mutant mice and reveal the importance of carrying out analyses of pheno-typic variation in a broad range of developmental stages. The present study contributes to the basic understanding of epigenetic relations among growing tissues and has di-rect implications for the field of paleoanthropology, where inferences about brain morphology are usually derived from skull remains.Los patrones de covariación entre rasgos fenotí-picos resultan de la acción de diversos procesos que se sola-pan durante el desarrollo. Los estudios experimentales cons-tituyen la aproximación más adecuada para evaluar el efecto de procesos específicos en la generación de tales patrones. El objetivo de este trabajo es analizar las interacciones entre rasgos morfológicos craneofaciales y cerebrales durante la vida prenatal tardía (18,5 días posconcepción) en ratones ex-puestos a desnutrición proteica materna. Se obtuvieron imá-genes del cráneo y cerebro a partir de microtomografía com-putada y se digitalizaron landmarks en 3D para cuantificar la forma y tamaño con técnicas de morfometría geométrica. Los resultados subrayan un efecto sistémico de la restricción proteica en el tamaño del cráneo y el cerebro. La forma del cráneo es parcialmente explicable por el tamaño cerebral y los patrones de variación en forma fueron sólo en parte coin-cidentes con los reportados antes para otras edades, lo cual sugiere que las trayectorias alométricas a lo largo de la vida pre- y posnatal cambian su dirección. Los rasgos de forma del neurocráneo y el esqueleto facial covariaron fuertemen-te, aunque se encontró una asociación débil entre la forma del cráneo y del cerebro. Estos resultados concuerdan con estudios previos en ratones mutantes y revelan la relevancia de analizar la variación fenotípica en distintas etapas. El pre-sente estudio contribuye al conocimiento básico de las inte-racciones epigenéticas entre tejidos en crecimiento y tiene implicancias en el campo paleoantropológico en el que las inferencias acerca de la morfología cerebral son usualmen-te derivadas del análisis del cráneo.Fil: Barbeito Andrés, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Gonzalez, Paula Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Hallgrimsson, Benedikt. University of Calgary; Canad

Growth Patterns and Shape Development of the Paediatric Mandible – a 3d Statistical Model

Background/Aim:To develop a 3D morphable model of the normal paediatric mandible to analyse shape development and growth patterns for males and females.Methods:Computed tomography (CT) data was collected for 242 healthy children referred for CT scan between 2011 and 2018 aged between 0 and 47 months (mean, 20.6 ± 13.4 months, 59.9% male). Thresholding techniques were used to segment the mandible from the CT scans. All mandible meshes were annotated using a defined set of 52 landmarks and processed such that all meshes followed a consistent triangulation. Following this, the mandible meshes were rigidly aligned to remove translation and rotation effects, whilst size effects were retained. Principal component analysis (PCA) was applied to the processed meshes to construct a generative 3D morphable model. Partial least squares (PLS) regression was also applied to the processed data to extract the shape modes with which to evaluate shape differences for age and gender. Growth curves were constructed for anthropometric measurements.Results:A 3D morphable model of the paediatric mandible was constructed and validated with good generalisation, compactness, and specificity. Growth curves of the assessed anthropometric measurements were plotted without significant differences between male and female subjects. The first principal component was dominated by size effects and is highly correlated with age at time of scan (Pearson’s r = 0.92, p < 0.01). As with PCA, the first extracted PLS mode captures much of the size variation within the dataset and is highly correlated with age (Pearson’s r = -0.9, p <0.01). Little correlation was observed between extracted shape modes and gender with either PCA or PLS for this study population.Conclusion:The presented 3D morphable model of the paediatric mandible enables an understanding of mandibular shape development and variation by age and gender. It allowed for the construction of growth curves, which contains valuable information that can be used to enhance our understanding of various disorders that affect the mandibular development. Knowledge of shape changes in the growing mandible has potential to improve diagnostic accuracy for craniofacial conditions that impact the mandibular morphology, objective evaluation, surgical planning, and patient follow-up

Growth Patterns and Shape Development of the Paediatric Mandible – a 3d Statistical Model

Background/Aim:To develop a 3D morphable model of the normal paediatric mandible to analyse shape development and growth patterns for males and females.Methods:Computed tomography (CT) data was collected for 242 healthy children referred for CT scan between 2011 and 2018 aged between 0 and 47 months (mean, 20.6 ± 13.4 months, 59.9% male). Thresholding techniques were used to segment the mandible from the CT scans. All mandible meshes were annotated using a defined set of 52 landmarks and processed such that all meshes followed a consistent triangulation. Following this, the mandible meshes were rigidly aligned to remove translation and rotation effects, whilst size effects were retained. Principal component analysis (PCA) was applied to the processed meshes to construct a generative 3D morphable model. Partial least squares (PLS) regression was also applied to the processed data to extract the shape modes with which to evaluate shape differences for age and gender. Growth curves were constructed for anthropometric measurements.Results:A 3D morphable model of the paediatric mandible was constructed and validated with good generalisation, compactness, and specificity. Growth curves of the assessed anthropometric measurements were plotted without significant differences between male and female subjects. The first principal component was dominated by size effects and is highly correlated with age at time of scan (Pearson’s r = 0.92, p < 0.01). As with PCA, the first extracted PLS mode captures much of the size variation within the dataset and is highly correlated with age (Pearson’s r = -0.9, p <0.01). Little correlation was observed between extracted shape modes and gender with either PCA or PLS for this study population.Conclusion:The presented 3D morphable model of the paediatric mandible enables an understanding of mandibular shape development and variation by age and gender. It allowed for the construction of growth curves, which contains valuable information that can be used to enhance our understanding of various disorders that affect the mandibular development. Knowledge of shape changes in the growing mandible has potential to improve diagnostic accuracy for craniofacial conditions that impact the mandibular morphology, objective evaluation, surgical planning, and patient follow-up

Growth patterns and shape development of the paediatric mandible – A 3D statistical model

BACKGROUND/AIM: To develop a 3D morphable model of the normal paediatric mandible to analyse shape development and growth patterns for males and females. METHODS: Computed tomography (CT) data was collected for 242 healthy children referred for CT scan between 2011 and 2018 aged between 0 and 47 months (mean, 20.6 ± 13.4 months, 59.9% male). Thresholding techniques were used to segment the mandible from the CT scans. All mandible meshes were annotated using a defined set of 52 landmarks and processed such that all meshes followed a consistent triangulation. Following this, the mandible meshes were rigidly aligned to remove translation and rotation effects, while size effects were retained. Principal component analysis (PCA) was applied to the processed meshes to construct a generative 3D morphable model. Partial least squares (PLS) regression was also applied to the processed data to extract the shape modes with which to evaluate shape differences for age and sex. Growth curves were constructed for anthropometric measurements. RESULTS: A 3D morphable model of the paediatric mandible was constructed and validated with good generalisation, compactness, and specificity. Growth curves of the assessed anthropometric measurements were plotted without significant differences between male and female subjects. The first principal component was dominated by size effects and is highly correlated with age at time of scan (Spearman's r = 0.94, p < 0.01). As with PCA, the first extracted PLS mode captures much of the size variation within the dataset and is highly correlated with age (Spearman's r = −0.94, p < 0.01). Little correlation was observed between extracted shape modes and sex with either PCA or PLS for this study population. CONCLUSION: The presented 3D morphable model of the paediatric mandible enables an understanding of mandibular shape development and variation by age and sex. It allowed for the construction of growth curves, which contains valuable information that can be used to enhance our understanding of various disorders that affect the mandibular development. Knowledge of shape changes in the growing mandible has potential to improve diagnostic accuracy for craniofacial conditions that impact the mandibular morphology, objective evaluation, surgical planning, and patient follow-up

Image processing for plastic surgery planning

This thesis presents some image processing tools for plastic surgery planning. In particular, it presents a novel method that combines local and global context in a probabilistic relaxation framework to identify cephalometric landmarks used in Maxillofacial plastic surgery. It also uses a method that utilises global and local symmetry to identify abnormalities in CT frontal images of the human body. The proposed methodologies are evaluated with the help of several clinical data supplied by collaborating plastic surgeons

Three-dimensional assessment of facial morphology in infants with cleft lip and palate

Differential growth was demonstrated between facial features and within some facial features. In particular, the columella, nostrils and philtrum did not grow significantly after surgery, although this would be considered normal in the age group studied. Facial growth in children with UCL and UCLP was independent of the head and body growth. The presence of a cleft of the secondary palate accentuated the amount of soft tissue disruption by the cleft in the lip and nose, but not the pattern of disruption. Primary lip / nose repair had no detrimental effect on the early growth and development of the facial features. Likewise, palate repair had no discernible effect on facial soft tissue growth at age 2 years. Primary lip /nose repair had a beneficial effect on facial morphology in terms of reducing asymmetry and was most successful in the improving philtrum and nasal base symmetry, less successful in improving the nasal rim asymmetry. A possible early beneficial effect of cleft repair remote from the surgery site was noted in the reduction of upper face asymmetry in the first year of life. Residual asymmetry in the facial features did not change by age 2 years, despite increases in size with growth. Facial morphology outcomes for UCL and UCLP children in this study was generally similar at 2 years of age, despite marked differences in pre-operative facial form. However, nasal base asymmetry, upper face asymmetry and residual nostril shape deformity were significantly greater in UCLP children at 2 years of age, than in UCL children. These shape differences were not detectable by measurement of facial dimensions alone

Virtual Morphology and Evolutionary Morphometrics in the new millenium.

EDITED VOLUME; abstract N/

Genetic architecture of craniofacial shape in the house mouse: a genetic and morphological perspective

Morphological diversity in nature is astounding. A remarkable example of such diversity is the vertebrate cranium. This structure is developmentally, anatomically, and functionally integrated with the many other tissues and sensory systems of the head. Because of this, it is under strong constrains to achieve an adult form (size and shape) compatible with the functional requirements of the individual. The genetic basis of craniofacial diversity has been traditionally studied from a macro-evolutionary perspective (i.e. at the between-species level), with special focus on adaptive radiation and domestication. The work presented in this thesis is an attempt to understand the genetic basis of craniofacial shape variation in the house mouse. By using between-subspecies and within population variation, I address the question from a micro-evolutionary perspective. In this thesis I also explore the genetic architecture of the traits (i.e. number, effect size, and genomic distribution of the causal loci), and the extent to which phenotypic variation can be explained by genetic variation – i.e. heritability of the traits. The first two chapters of this thesis are the first genome-wide approximation to the genetic architecture of craniofacial shape and size in mice. I combine highly recombinant mouse populations –wild hybrid mice and outbred lab mice- with dense marker coverage of the genome to map the loci underlying phenotypic variation. I identify genes previously known to be involved in craniofacial formation, and provide a list of genomic regions that contain new candidate genes for craniofacial development. Regarding the genetic architecture, I show that craniofacial traits are highly polygenic and highly heritable, with many loci of very small effect distributed uniformly along the genome. The last chapter of the thesis is an assessment of the morphological transition associated with the degree of admixture between two subspecies of the house mouse, Mus musculus musculus and Mus musculus domesticus. I show that craniofacial shape changes, but not size changes, are correlated with the level of admixture. The transition from M. m. musculus to M. m. domesticus is continuous, such mode would be expected from a trait with polygenic architecture, and therefore these results are in line with the genetic results obtained in previous chapters. Overall the work presented in this thesis is the first genome-wide analyses of the genetic basis and genetic architecture of craniofacial shape variation in the house mouse. It is also the first time shape variation is explored in a close-to-natural context; previous work used crosses between inbred 10 mouse strains. Therefore, the results reported here are directly relevant to the understanding of complex traits evolution

Ancestral variation in mid-craniofacial morphology in a South African sample

Ancestry estimation is a critical component of the demographic profile compiled by forensic anthropologists when unknown skeletal remains are discovered. The mid-craniofacial region is most frequently used to estimate ancestry as this region reflects the genetic and morphological ancestry of an individual. The diverse composition of the South African population makes ancestry estimation problematic, and necessitates the development of reliable, population-specific standards. This study sought to characterise variations in mid-craniofacial shape and size between South Africans of European ancestry (EA), African ancestry (AA) and Mixed ancestry (MA). Metric, nonmetric and geometric morphometric assessments were performed on 392 crania from skeletal collections in South Africa. Variations in mid-craniofacial shape and size were assessed in the orbital, nasal, zygomatic and maxillary regions in two-and three-dimensions. Univariate and multivariate statistical analyses were employed to characterise variation and estimate ancestry in AA, MA and EA individuals. Multivariate analyses suggest that tightly integrated ancestral variations in each component of the mid-craniofacial region are associated with functional, regional and developmental proximities of these regions. Specifically, AA individuals exhibited wider and shorter midfacial regions than EA individuals, who exhibited the narrowest orbital, zygomatic and nasal breadths and the longest upper facial, orbital and nasal heights. EA individuals exhibited inferiorly-angled orbits, elongated nasal apertures and anteriorly projecting nasal bridges. Rounder nasal apertures, less anteriorly projecting nasal bridges and more anteriorly projecting maxillary regions were detected in AA individuals. MA individuals exhibited heterogeneity in terms of craniofacial shape and size, and therefore produced the lowest ancestry estimation accuracies. Overall, nasal and maxillary regions were the most ancestrally diverse regions. Antemortem maxillary tooth loss and midfacial trauma were confounding factors in ancestry estimation accuracies. The lowest ancestry estimation accuracies were yielded by two-dimensional metric (27%-60.2%) and nonmetric (57.1%-82.4%) methods. Metric and geometric morphometric assessments yielded the highest repeatability (≥ 95%) indicating that these methods may be more reliable for use in medicolegal contexts. Geometric morphometric shape assessments yielded the highest ancestry estimation accuracies (75-97.9%), suggesting the presence of three dimensional shape variations between ancestry groups. These results suggest that a continuum of ancestral variation, with large areas of overlap, exists across South African populations and emphasises the need to develop multivariate ancestry estimation standards which can estimate ancestry reliably

New approaches in the virtual reconstruction of fragmented specimen

Das Hauptaugenmerk dieser Arbeit liegt auf der virtuellen Rekonstruktion von Schädeln, die sich durch das Fehlen eines großen Teils der Schädelknochen auszeichnen. Mithilfe von Methoden der virtuellen Anthropologie und Geometrischen Morphometrie kann dabei eine Vielzahl von Problemen konfrontiert werden, die während der Rekonstruktion von fragmentierten fossilen Schädeln entstehen können. Denn jede Schädelrekonstruktion weisst generell eine gewisse Ungenauigkeit auf. Diese wird von verschiedenen Faktoren beeinflusst, z.B. Größe der fehlenden Schädelteile oder der Rekonstruktionsmethode. Ein Schwerpunkt dieser Arbeit liegt deshalb in der Untersuchung der Auswirkungen verschiedener Faktoren auf die Ungenauigkeit fossiler Rekonstruktionen mithilfe von landmarks und semilandmarks. Darüber hinaus werden neue Ansätze für die anatomische Rekonstruktion von stark beschädigten Schädeln eingeführt. Bei der Rekonstruktion von fossilen Schädelfragmenten in einer virtuellen Umgebung wird jeder einzelne Schritt in einem ausführlichen Protokoll gespeichert. Dies ermöglicht die Erstellung einer großen Anzahl von verschiedenen Rekonstruktionen. Da eine Rekonstruktion niemals perfekt sein wird, berücksichtigt dieser Ansatz das mangelnde Wissen darüber, wie das Original-Indiviuum wirklich aussah. Mit anderen Worten zeichnet sich jede Rekonstruktion durch einen gewissen Grad an Ungenauigkeit aus. Die Ermittlung dieser Ungenauigkeit ist umso wichtiger, da heute hohe Maßstäbe an die Qualität von virtuellen Modellen gestellt werden, die in unterschiedlichen Studien der Ontogenie, Phylogenie und Biomechanik eingesetzt werden. Ich veranschauliche diese Ansätze durch die Rekonstruktion mehrerer virtuell fragmentierter Individuen und wende die gewonnenen Informationen unter anderem in der Rekonstruktion des Australopithecus afarensis Individuums A.L. 444-2 an. Desweiteren untersuche ich die morphologische Integration im kraniofazialen Komplex von Individuen der Überfamilie Hominoidea, um Kovariationsmuster aufzuzeigen, die während der Schätzung der Ungenauigkeit von anatomischen Rekonstruktionen von potenzieller Hilfe sein konnten.The main theme of this thesis is how different scenarios of missing data estimation influence the uncertainty of virtual reconstructions. Using a combination of tools from Virtual Anthropology and Geometrics Morphometrics, a variety of problems is approached comprising major problems that arise during the anatomical reassembly of fragmented fossil crania and the geometrical reconstruction of missing data. The focus is on the quantitavive description of accuracies and uncertainties in fossil reconstructions using landmarks and semilandmarks from different reference samples. Furthermore, new approaches for the anatomical reconstruction of severly damaged crania are introduced. When dealing with the reassembly of fragments in a virtual environment, every single step can be saved in a detailed protocol and used as a basis for subsequent modifications. This creates a large number of different reconstructions, considering the uncertainty of the reconstruction itself. Reconstructions of incomplete fossil specimens are needed in varying contexts from studies of ontogeny, phylogeny or biomechanics. I exemplify these approaches by reconstructing several virtually fragmented specimens from extant and extinct species, and applying part of this information to the Australopithecus afarensis specimens A.L. 444-2. Furthermore I investigate morphological integration in the hominoid craniofacial complex, showing patterns of covariation that could be of potential help estimating the uncertainty in the anatomical reconstruction of fragmented specimens