ABSTRACT
The pterion is the sutural juncture of the frontal, parietal, sphenoidal, temporal, and zygomatic bones on the lateral aspect of the cranium. As a craniometric landmark, the pterion has a taxonomic valence, in addition to a common neurosurgical entry point in medicine. Variation in the articulation patterns at the pterion have been documented between primate species yet have a high degree of uniformity within species, suggesting a genetic control for this complex region of the skull. In this study, pterion pattern variation was investigated in 1627 Rhesus macaque crania of the Cayo Santiago colony. The colony's associated skeletal collections accompany known age, sex, and maternal lineages. Pterion pattern prevalence rates were tested against matrilines, as well as cranial shape, and cranial sutural fusion ages (including individuals with prematurely fused sutures). Five patterns were identified, the most prominent being the prevailing Old World Monkey frontotemporal (FT) articulation (83.4%). The relative frequency of those not exhibiting the FT pattern was found to vary considerably between matrilineal families (p = 0.037), ranging from 5.3% to 34.2%. Mothers with the non-FT pterion pattern were three times as likely to bear non-FT offspring. Cranial shape additionally varied with pterion type. Males exhibiting zygomaticotemporal (ZT) and sphenoparietal (SP) articulations possessed a relatively longer and narrower cranium than those with the default FT type (p = < 0.001). Cranial sutural fusion ages were not found to differ between pterion types, though all individuals with craniosynostosis (6; 0.38%) exhibited the FT type. The study provided strong evidence for a genetic source for pterion pattern as well as outlining a relatively novel relationship with cranial shape and sutural fusion ages. A unifying explanation may lie in those genes involved in both sutural and craniofacial development, or in the variation of brain growth processes channeling sutural articulation at the pterion. Both may be heritable and responsible for producing observed matrilineal differences in the pterion.
Subject(s)
Cranial Sutures , Macaca mulatta , Skull , Animals , Macaca mulatta/anatomy & histology , Male , Female , Skull/anatomy & histology , Cranial Sutures/anatomy & histology , Cranial Sutures/growth & development , CephalometryABSTRACT
SUMMARY: Facial sutures contribute significantly to postnatal facial development, but their potential role in craniofacial disease is understudied. Since interest in their development and physiology peaked in the mid-twentieth century, facial sutures have not garnered nearly the same clinical research interest as calvarial sutures or cranial base endochondral articulations. In addition to reinforcing the complex structure of the facial skeleton, facial sutures absorb mechanical stress and generally remain patent into and beyond adolescence, as they mediate growth and refine the shape of facial bones. However, premature closure of these sites of postnatal osteogenesis leads to disrupted growth vectors and consequent dysmorphologies. Although abnormality in individual sutures results in isolated facial deformities, we posit that generalized abnormality across multiple sutures may be involved in complex craniofacial conditions such as syndromic craniosynostosis. In this work, the authors comprehensively review 27 key facial sutures, including physiologic maturation and closure, contributions to postnatal facial development, and clinical consequences of premature closure.
Subject(s)
Cranial Sutures/growth & development , Craniosynostoses/physiopathology , Facial Bones/growth & development , HumansABSTRACT
BACKGROUND: The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth. METHODS: In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously-deleted mice (Twist1+/-) with micro-computed tomographic images. RESULTS: In Twist1+/- mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1+/- mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1+/- mouse. In one postnatal day 56 Twist1+/- mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified. CONCLUSION: The authors'results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis. CLINICAL RELEVANCE STATEMENT: The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.
Subject(s)
Acrocephalosyndactylia/diagnosis , Cranial Sutures/diagnostic imaging , Frontal Bone/diagnostic imaging , Twist-Related Protein 1/genetics , Zygoma/diagnostic imaging , Acrocephalosyndactylia/genetics , Animals , Cranial Sutures/abnormalities , Cranial Sutures/growth & development , Disease Models, Animal , Female , Frontal Bone/abnormalities , Frontal Bone/growth & development , Gene Expression Regulation, Developmental , Heterozygote , Humans , Male , Mice , Mice, Transgenic , Mutation , X-Ray Microtomography , Zygoma/abnormalities , Zygoma/growth & developmentABSTRACT
Craniofacial development depends on formation and maintenance of sutures between bones of the skull. In sutures, growth occurs at osteogenic fronts along the edge of each bone, and suture mesenchyme separates adjacent bones. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure. Seven populations at E16.5 and nine at E18.5 comprise the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog signaling, marks a mesenchymal population distinct from those of other neurocranial sutures. Tracing of the neonatal Hhip-expressing population shows that descendant cells persist in the coronal suture and contribute to calvarial bone growth. In Hhip-/- coronal sutures at E18.5, the osteogenic fronts are closely apposed and the suture mesenchyme is depleted with increased hedgehog signaling compared to those of the wild type. Collectively, these data demonstrate that Hhip is required for normal coronal suture development.
Subject(s)
Carrier Proteins/metabolism , Cranial Sutures/growth & development , Hedgehog Proteins/metabolism , Membrane Glycoproteins/metabolism , Single-Cell Analysis/methods , Animals , Bone Development , Carrier Proteins/genetics , Cell Proliferation , Cranial Sutures/pathology , Craniosynostoses , DNA Topoisomerases, Type II , Female , Gene Expression Regulation, Developmental , Male , Membrane Glycoproteins/genetics , Mesoderm , Mice , Mice, Inbred C57BL , Osteogenesis/genetics , Osteogenesis/physiology , Phenotype , Poly-ADP-Ribose Binding Proteins , Sequence Analysis, RNA , Signal Transduction , Skull , TranscriptomeABSTRACT
BACKGROUND: Fusion of cranial-base sutures/synchondroses presents a clinical conundrum, given their often unclear "normal" timing of closure. This study investigates the physiologic fusion timelines of cranial-base sutures/synchondroses. METHODS: Twenty-three age intervals were analyzed in subjects aged 0 to 18 years. For each age interval, 10 head computed tomographic scans of healthy subjects were assessed. Thirteen cranial-base sutures/synchondroses were evaluated for patency. Partial closure in greater than or equal to 50 percent of subjects and complete bilateral closure in less than 50 percent of subjects defined the fusion "midpoint." Factor analysis identified clusters of related fusion patterns. RESULTS: Two hundred thirty scans met inclusion criteria. The sutures' fusion midpoints and completion ages, respectively, were as follows: frontoethmoidal, 0 to 2 months and 4 years; frontosphenoidal, 6 to 8 months and 12 years; and sphenoparietal, 6 to 8 months and 4 years. Sphenosquamosal, sphenopetrosal, parietosquamosal, and parietomastoid sutures reached the midpoint at 6 to 8 months, 8 years, 9 to 11 months, and 12 years, respectively, but rarely completed fusion. The occipitomastoid suture partially closed in less than or equal to 30 percent of subjects. The synchondroses' fusion midpoints and completion ages, respectively, were as follows: sphenoethmoidal, 3 to 5 months and 5 years; spheno-occipital, 9 years and 17 years; anterior intraoccipital, 4 years and 10 years; and posterior intraoccipital, 18 to 23 months and 4 years. The petro-occipital synchondrosis reached the midpoint at 11 years and completely fused in less than 50 percent of subjects. Order of fusion of the sutures, but not the synchondroses, followed the anterior-to-posterior direction. Factor analysis suggested three separate fusion patterns. CONCLUSIONS: The fusion timelines of cranial-base sutures/synchondroses may help providers interpret computed tomographic data of patients with head-shape abnormalities. Future work should elucidate the mechanisms and sequelae of cranial-base suture fusion that deviates from normal timelines.
Subject(s)
Cranial Sutures/growth & development , Skull Base/growth & development , Adolescent , Child , Child, Preschool , Cranial Sutures/diagnostic imaging , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Skull Base/diagnostic imaging , Time Factors , Tomography, X-Ray Computed/statistics & numerical dataABSTRACT
RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, and playing a specific role in craniofacial and skull morphogenesis. The anatomically modern human (AMH) features sequence changes in the RUNX2 locus compared with archaic hominins' species. We aimed to understand how these changes may have contributed to human skull globularization occurred in recent evolution. We compared in silico AMH and archaic hominins' genomes, and used mesenchymal stromal cells isolated from skull sutures of craniosynostosis patients for in vitro functional assays. We detected 459 and 470 nucleotide changes in noncoding regions of the AMH RUNX2 locus, compared with the Neandertal and Denisovan genomes, respectively. Three nucleotide changes in the proximal promoter were predicted to alter the binding of the zinc finger protein Znf263 and long-distance interactions with other cis-regulatory regions. By surface plasmon resonance, we selected nucleotide substitutions in the 3'UTRs able to affect miRNA binding affinity. Specifically, miR-3150a-3p and miR-6785-5p expression inversely correlated with RUNX2 expression during in vitro osteogenic differentiation. The expression of two long non-coding RNAs, AL096865.1 and RUNX2-AS1, within the same locus, was modulated during in vitro osteogenic differentiation and correlated with the expression of specific RUNX2 isoforms. Our data suggest that RUNX2 may have undergone adaptive phenotypic evolution caused by epigenetic and post-transcriptional regulatory mechanisms, which may explain the delayed suture fusion leading to the present-day globular skull shape.
Subject(s)
Biological Evolution , Core Binding Factor Alpha 1 Subunit/genetics , Skull/anatomy & histology , Animals , Core Binding Factor Alpha 1 Subunit/metabolism , Cranial Sutures/growth & development , Craniosynostoses/genetics , Epigenesis, Genetic , Genome, Human , Hominidae/anatomy & histology , Hominidae/genetics , Humans , Mesenchymal Stem Cells , MicroRNAs/genetics , Neanderthals/anatomy & histology , Neanderthals/genetics , Osteogenesis/genetics , RNA, Long Noncoding/geneticsABSTRACT
The cranial bones constitute the protective structures of the skull, which surround and protect the brain. Due to the limited repair capacity, the reconstruction and regeneration of skull defects are considered as an unmet clinical need and challenge. Previously, it has been proposed that the periosteum and dura mater provide reparative progenitors for cranial bones homeostasis and injury repair. In addition, it has also been speculated that the cranial mesenchymal stem cells reside in the perivascular niche of the diploe, namely, the soft spongy cancellous bone between the interior and exterior layers of cortical bone of the skull, which resembles the skeletal stem cells' distribution pattern of the long bone within the bone marrow. Not until recent years have several studies unraveled and validated that the major mesenchymal stem cell population of the cranial region is primarily located within the suture mesenchyme of the skull, and hence, they are termed suture mesenchymal stem cells (SuSCs). Here, we summarized the characteristics of SuSCs, this newly discovered stem cell population of cranial bones, including the temporospatial distribution pattern, self-renewal, and multipotent properties, contribution to injury repair, as well as the signaling pathways and molecular mechanisms associated with the regulation of SuSCs.
Subject(s)
Bone Regeneration/genetics , Cranial Sutures/cytology , Mesenchymal Stem Cells/cytology , Osteocytes/cytology , Skull Fractures/genetics , Animals , Axin Protein/genetics , Axin Protein/metabolism , Cathepsin K/genetics , Cathepsin K/metabolism , Cell Differentiation , Cell Proliferation , Cranial Sutures/growth & development , Cranial Sutures/injuries , Cranial Sutures/metabolism , Craniosynostoses/genetics , Craniosynostoses/metabolism , Craniosynostoses/pathology , Gene Expression Regulation , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Osteocytes/metabolism , Signal Transduction , Skull Fractures/metabolism , Skull Fractures/pathology , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein GLI1/metabolismABSTRACT
RESUMEN: Objetivo: Evaluar la maduración de la sutura palatina media en adolescentes y adultos jóvenes chilenos, mediante valoración morfológica de imágenes de tomografía computarizada de haz cónico del maxilar. Material y método: Se analizó la sutura palatina media de 150 sujetos entre 15 y 30 años, seleccionados desde la base de datos radiológicos de un centro universitario de salud. La maduración sutural fue evaluada en el corte axial, utilizando el método de Angelieri y cols., clasificándola en cinco etapas (A, B, C, D y E). Se utilizaron las pruebas de correlación de Pearson para medir la concordancia intra e interexaminador, y T-Student para las diferencias entre sexos. Resultados: El estado de maduración más frecuente fue C (43,3%), seguido por E (33,3%) y D (22%). En hombres, la etapa C fue más frecuente (49%), mientras que en mujeres fue la etapa E (39%). Sin embargo, no se encontraron diferencias estadísticamente significativas entre ambos sexos. Conclusiones: Aunque la mayoría de la muestra presentó una etapa tardía de maduración sutural, el 45% presentó estados de maduración sutural donde sería posible la expansión de naturaleza no quirúrgica. Debido a la variabilidad observada en adolescentes y adultos jóvenes, se recomienda la evaluación individual con imagenología 3D.
ABSTRACT: Objective: To evaluate midpalatal suture maturation in Chilean adolescents and young adults through morphological assessment of cone-beam computed tomography images of the maxilla. Materials and methods: Analysis of the midpalatal suture of 150 subjects aged between 15 and 30 was performed, selected from a university clinical center radiological database. Sutural maturation was evaluated in the axial cross-section, using the method described by Angelieri et al., classifying it in five stages (A, B, C, D and E). Pearson's correlation tests were used to assess intra- and inter-examiner agreement, and T-Student for assessing differences between genders. Results: The most frequent maturation stage was C (43.3%), followed by E (33.3%) and D (22%). In men, stage C was more frequent (49%), while in women it was stage E (39%). However, no statistically significant differences were found between genders. Conclusions: Although the majority of the sample presented a late stage of sutural maturation, 45% presented states of sutural maturation where the expansion of a non-surgical nature would be possible. Due to the variability observed in adolescents and young adults, individual evaluation with 3D imaging is recommended.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Cranial Sutures/growth & development , Cranial Sutures/diagnostic imaging , Palate, Hard/growth & development , Palate, Hard/diagnostic imaging , Chile , Cross-Sectional Studies , Palatal Expansion Technique , Maxilla/growth & development , Maxilla/diagnostic imagingABSTRACT
Cranial synchondroses are cartilaginous joints between basicranial bones or between basicranial bones and septal cartilage, and have been implicated as having a potential active role in determining craniofacial form. However, few studies have examined them histologically. Using histological and immunohistochemical methods, we examined all basicranial joints in serial sagittal sections of newborn heads from nine genera of primates (five anthropoids, four strepsirrhines). Each synchondrosis was examined for characteristics of active growth centers, including a zonal distribution of proliferating and hypertrophic chondrocytes, as well as corresponding changes in matrix characteristics (i.e., density and organization of Type II collagen). Results reveal three midline and three bilateral synchondroses possess attributes of active growth centers in all species (sphenooccipital, intrasphenoidal, presphenoseptal). One midline synchondrosis (ethmoseptal) and one bilateral synchondrosis (alibasisphenoidal synchondrosis [ABS]) are active growth centers in some but not all newborn primates. ABS is oriented more anteriorly in monkeys compared to lemurs and bushbabies. The sphenoethmoidal synchondrosis (SES) varies at birth: in monkeys, it is a suture-like joint (i.e., fibrous tissue between the two bones); however, in strepsirrhines, the jugum sphenoidale is ossified while the mesethmoid remains cartilaginous. No species possesses an SES that has the organization of a growth plate. Overall, our findings demonstrate that only four midline synchondroses have the potential to actively affect basicranial angularity and facial orientation during the perinatal timeframe, while the SES of anthropoids essentially transitions toward a "suture-like" function, permitting passive growth postnatally. Loss of cartilaginous continuity at SES and reorientation of ABS distinguish monkeys from strepsirrhines.
Subject(s)
Cartilage/growth & development , Cranial Sutures/growth & development , Skull/growth & development , Strepsirhini/growth & development , Animals , Animals, Newborn , Osteogenesis/physiologyABSTRACT
Sutures, the thin, soft tissue between skull bones, serve as the major craniofacial growth centers during postnatal development. In a newborn skull, the sutures are straight; however, as the skull develops, the sutures wind dynamically to form an interdigitation pattern. Moreover, the final winding pattern had been shown to have fractal characteristics. Although various molecules involved in suture development have been identified, the mechanism underlying the pattern formation remains unknown. In a previous study, we reproduced the formation of the interdigitation pattern in a mathematical model combining an interface equation and a convolution kernel. However, the generated pattern had a specific characteristic length, and the model was unable to produce a fractal structure with the model. In the present study, we focused on the anterior part of the sagittal suture and formulated a new mathematical model with time-space-dependent noise that was able to generate the fractal structure. We reduced our previous model to represent the linear dynamics of the centerline of the suture tissue and included a time-space-dependent noise term. We showed theoretically that the final pattern from the model follows a scaling law due to the scaling of the dispersion relation in the full model, which we confirmed numerically. Furthermore, we observed experimentally that stochastic fluctuation of the osteogenic signal exists in the developing skull, and found that actual suture patterns followed a scaling law similar to that of the theoretical prediction.
Subject(s)
Cranial Sutures/growth & development , Animals , Fractals , Humans , Infant, Newborn , Mice , Models, Biological , Models, Theoretical , Morphogenesis/physiology , Osteogenesis/physiologyABSTRACT
BACKGROUND: Cone beam computed tomography (CBCT) imaging techniques are the recent rage in the field of oral diagnostic imaging modality. It is noninvasive, faster and lacks anatomic superimposition. Earlier maxillary occlusal radiographs were used to assess and evaluate the mid palatal suture, but being a two dimensional imaging modality it could not assess the ossification process which takes place in multiple planes mostly due to curved nature of the palate. In this study we assessed the mid palatal suture morphology and classify them according to the variants using CBCT images. MATERIALS AND METHODS: A total of 200 CBCT scans (95 males and 105 females) were evaluated in the present study from the archives of an imaging center. As per Angelieri classification the midpalatal suture was classified into five categories (A-E) depending on the degree of ossification that had taken place. Statistical analysis was done by Chi Square test using SPSS version 23.0. RESULTS: There is statistically significant difference present in the stages of maturity of mid palatal suture in various age groups with Stage B is most common in Group 1 (50%), Stage C most common in Group 2 (60%) and Group 3 (40%) and Stage E more common in Group 4 (50%). CONCLUSION: The results of the present study showed a wide variation in the initiation time and the degree of ossification and morphology of the midpalatal suture in different age groups. Although there was an increase in the closure of the suture with aging, age is not a reliable criterion for determining the open or closed nature of the suture. This finding is important in providing an idea as to how diverse is the ossification of maxillary sutures.
Subject(s)
Cone-Beam Computed Tomography/methods , Cranial Sutures/diagnostic imaging , Palate/diagnostic imaging , Adolescent , Adult , Anatomic Variation , Child , Cranial Sutures/growth & development , Female , Humans , Male , Palate/growth & developmentABSTRACT
PURPOSE: Incisive suture is a suture classically described on the oral face of the palate in fetuses and young children. The aim of our study was to describe the evolution of the incisive suture in human fetuses and to evaluate the incidence of this suture in a population of young children under 4 years, to determine if there is a possibility of improving the anterior growth of the maxilla, by stimulation of this suture. METHODS: One hundred and thirty CT scan images of patients aged from birth to 48 months have been studied and nine fetal palates aged from 18 to 26 weeks of development, have been scanned using high-resolution X-ray micro-computed tomography RESULTS: The CT scan images of patients showed that an incisive suture was present in 33/130 cases (25,4%). All the patients with a suture were under 2 years old. The fetal palate study showed that the suture was present in the inferior aspect of the palate (oral cavity) in all cases. The incisive suture increased from 18 to 24 weeks. At 26 weeks it stopped growing although the intercanine length increased. Considering the closure of the suture in a vertical plane, our study on fetuses has shown that the incisive suture is closing from its superior side (nasal side) to its inferior side. CONCLUSIONS: Considering all these results it appears to us that the incisive suture is partially ossified after birth, it cannot be stimulated by orthodontic appliances.
Subject(s)
Cranial Sutures/abnormalities , Fetal Development , Maxilla/abnormalities , Maxillofacial Abnormalities/epidemiology , Palate, Hard/abnormalities , Child, Preschool , Cranial Sutures/diagnostic imaging , Cranial Sutures/growth & development , Female , Fetus/diagnostic imaging , Gestational Age , Humans , Incidence , Infant , Male , Maxilla/diagnostic imaging , Maxilla/growth & development , Maxillofacial Abnormalities/diagnosis , Palatal Expansion Technique , Palate, Hard/diagnostic imaging , Palate, Hard/growth & developmentABSTRACT
PURPOSE: The aim of this study was to classify the maturation of the midpalatal suture (MPS) in a sample of individuals aged 15 years and older. METHODS: Tomographic images in axial sections of the MPS of 289 female individuals and 198 male individuals aged between 15 and 40 years were analyzed and classified in stages of maturation (A, B, C, D, and E), stage A represents the earliest maturation stage of the suture and in stage E the fusion of the MPS has occurred in the maxilla. The Kruskal-Wallis and Student-Newman-Kells tests were used to compare the chronological ages among different maturation stages. Spearman's correlation coefficient was used to assess the correlation between patient's age and the maturation stages of the MPS. RESULTS: Stage A was not observed in the sample. Stages B and C represent, respectively, 1.03% and 34.09% of the sample, stage D was found in 16.63% of the sample while stage E was the most prevalent stage found (48.25%). For females, it was revealed no statistically significant difference in the mean ages among stages C, D and E (p = 0.4753). For males, a statistically significant difference was observed, with the mean age of individuals in stages D and E of the MPS maturation higher than in other stages (p = 0.0001). There was a significant, but weak, correlation between patient's age and the maturation stages of the suture (rs = 0.11/p = 0.01). CONCLUSION: No individuals in stage A of suture maturation were found and stage B was identified in only 1% of the sample. The majority of the patients (64.88%) presented at least partial fusion of the MPS (stages D and E).
Subject(s)
Cone-Beam Computed Tomography , Cranial Sutures/growth & development , Palate, Hard/growth & development , Adolescent , Adult , Age Factors , Cranial Sutures/diagnostic imaging , Female , Humans , Male , Malocclusion/surgery , Palatal Expansion Technique , Palate, Hard/diagnostic imaging , Young AdultABSTRACT
The aim of this study is to quantify and statistically model the age-related decline in the fibrous connective tissue interface of the anterior fontanelle in modern Australian infants, using three-dimensional, semi-automated computed-assisted design protocols. Non-linear regression with variance models, using power functions, combined with quantile regression of the 5th and 95th population percentiles, were utilised to assess absolute anterior fontanelle surface area (AFSA) as a function of age, using multi-slice cranial computed tomography scans obtained from 256 infants aged < 30 months (males: n = 126, females: n = 109) from Brisbane children's hospitals. Normalised AFSA (NFSA), standardised for variation in cephalic size, followed a progressive decline from birth, the greatest velocity change occurring between the 3-6 and 6-9 month cohorts. Growth of the neurocranium is the most significant within the first 8 months postpartum, with a mean increase of 19.03 mm in maximum cranial length and 10.04 mm in breadth. Directionality of fontanelle closure, quantified using spline curves refutes fundamental assumptions that the anterior fontanelle is consistent with a quadrilateral, and contiguous sutures exhibit constant velocity of closure. The present study provides normative values for fontanelle size and diameters as well as new predictive non-linear models for age substantiation, screening of developmental abnormalities and indicators of suspected child maltreatment in modern infants aged birth to 30 months.
Subject(s)
Cranial Fontanelles/growth & development , Cranial Sutures/growth & development , Australia , Child, Preschool , Computer Simulation , Cranial Fontanelles/diagnostic imaging , Cranial Sutures/diagnostic imaging , Female , Humans , Infant , Infant, Newborn , Male , Models, Anatomic , Reference Values , Tomography, X-Ray ComputedABSTRACT
Cranial suture closure has been recognized for over a century as a useful trait for age estimation. Although this indicator has become a standard feature of age assessment protocols in skeletal remains, serious questions have been raised about its reliability. This article attempts to provide a comprehensive review of cranial suture closure as an age indicator from several perspectives, including its anatomy and history, as well as issues relating to validation, statistics, and the potential of technological advancements to improve outcomes. We further suggest a path forward for the use of cranial suture closure as an estimator of age. Although its unreliability has been widely reported, cranial suture closure still appears to have value as an aging method, and it is hoped that the information contained in this article can serve as a stepping stone toward more effective use of this indicator. The cranium is often more durable than other skeletal elements in both archaeological and forensic circumstances, so maximizing the effectiveness of cranial indicators is an important goal. It is hoped that recent advancements in technology and in analytical approaches to the cranial sutures could breathe some new life into this feature as an indicator of age.
Subject(s)
Age Determination by Skeleton/methods , Cranial Sutures/growth & development , Cranial Sutures/diagnostic imaging , Forensic Anthropology/methods , History, 20th Century , History, 21st Century , Humans , Osteogenesis , Statistics as Topic , Tomography, X-Ray ComputedABSTRACT
Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis.
Subject(s)
Cranial Sutures/growth & development , Craniosynostoses/pathology , Skull/cytology , Child, Preschool , Computer Simulation , Craniosynostoses/diagnostic imaging , Craniosynostoses/surgery , Craniotomy , Finite Element Analysis , Humans , Image Processing, Computer-Assisted , Infant , Infant, Newborn , Longitudinal Studies , Retrospective Studies , Skull/diagnostic imaging , Tomography, X-Ray Computed/methodsABSTRACT
Mechanical force across sutures is able to promote suture osteogenesis. Orthodontic clinics often use this biological characteristic of sutures to treat congenital cranio-maxillofacial malformations. However, the underlying mechanisms still remain poorly understood. Craniofacial sutures provide a special growth source and support primary sites of osteogenesis. Here, we isolated rat sagittal suture cells (rSAGs), which had mesenchymal stem cell characteristics and differentiating abilities. Cells were then subjected to mechanical tension (5% elongation, 0.5 Hz; sinusoidal waveforms) showing that mechanical tension could enhance osteogenic differentiation but hardly affect proliferation of rSAGs. Besides, mechanical tension could increase Rho-associated kinase (ROCK) expression and enhance transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation. Inhibiting ROCK expression could suppress tension-induced osteogenesis and block tension-induced upregulation of nuclear TAZ. In addition, our results indicated that TAZ had direct combination sites with runt-related transcription factor 2 (Runx2) in rSAGs, and knock-downed TAZ simultaneously decreased the expression of Runx2 no matter with or without mechanical tension. In summary, our findings demonstrated that the multipotency of rSAGs in vitro could give rise to early osteogenic differentiation under mechanical tension, which was mediated by ROCK-TAZ signal axis.
Subject(s)
Core Binding Factor Alpha 1 Subunit/genetics , Cranial Sutures/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Osteogenesis/genetics , Trans-Activators/genetics , rho-Associated Kinases/genetics , Animals , Cell Differentiation/genetics , Cranial Sutures/growth & development , Cranial Sutures/pathology , Mechanical Phenomena , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Rats , Signal Transduction/genetics , Transcriptional Coactivator with PDZ-Binding Motif ProteinsABSTRACT
Sagittal craniosynostosis (SCS), the most common type of premature perinatal cranial suture fusion, results in abnormal head shape that requires extensive surgery to correct. It is important to find objective and repeatable measures of severity and surgical outcome to examine the effect of timing and technique on different SCS surgeries. The purpose of this study was to develop statistical models of infant (0-6 months old) skull growth in both normative and SCS subjects (prior to surgery). Our goal was to apply these models to the assessment of differences between these two groups in overall post-natal growth patterns and sutural growth rates as a first step to develop methods for predictive models of surgical outcome. We identified 81 patients with isolated, non-syndromic SCS from Seattle Children's Craniofacial Center patient database who had a preoperative CT exam before the age of 6 months. As a control group, we identified 117 CT exams without any craniofacial abnormalities or bone fractures in the same age group. We first created population-level templates from the CT images of the SCS and normal groups. All CT images from both groups, as well as the canonical templates of both cohorts, were annotated with anatomical landmarks, which were used in a growth model that predicted the locations of these landmarks at a given age based on each population. Using the template images and the landmark positions predicted by the growth models, we created 3D meshes for each week of age up to 6 months for both populations. To analyze the growth patterns at the suture sites, we annotated both templates with additional semi-landmarks equally spaced along the metopic, coronal, sagittal and lambdoidal cranial sutures. By transferring these semi-landmarks to meshes produced from the growth model, we measured the displacement of the bone borders and suture closure rates. We found that the growth at the metopic and coronal sutures were more rapid in the SCS cohort than in the normal cohort. The antero-posterior displacement of the semi-landmarks also indicated a more rapid growth in the sagittal plane in the SCS model than in the normal model. Statistical templates and geometric morphometrics are promising tools for understanding the growth patterns in normal and synostotic populations and to produce objective and reproducible measurements of severity and outcome. Our study is the first of its kind to quantify the bone growth for the first 6 months of life in both normal and sagittal synostosis patients.
Subject(s)
Cranial Sutures/growth & development , Craniosynostoses/diagnostic imaging , Skull/growth & development , Cranial Sutures/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Infant , Infant, Newborn , Male , Skull/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
The vertebrate skull varies widely in shape, accommodating diverse strategies of feeding and predation. The braincase is composed of several flat bones that meet at flexible joints called sutures. Nearly all vertebrates have a prominent 'coronal' suture that separates the front and back of the skull. This suture can develop entirely within mesoderm-derived tissue, neural crest-derived tissue, or at the boundary of the two. Recent paleontological findings and genetic insights in non-mammalian model organisms serve to revise fundamental knowledge on the development and evolution of this suture. Growing evidence supports a decoupling of the germ layer origins of the mesenchyme that forms the calvarial bones from inductive signaling that establishes discrete bone centers. Changes in these relationships facilitate skull evolution and may create susceptibility to disease. These concepts provide a general framework for approaching issues of homology in cases where germ layer origins have shifted during evolution.
Subject(s)
Biological Evolution , Mesoderm/growth & development , Neural Crest/growth & development , Skull/growth & development , Animals , Cranial Sutures/growth & development , Cranial Sutures/pathology , Humans , Skull/pathologyABSTRACT
The transcription factor 12 (tcf12) is a basic Helix-Loop-Helix protein (bHLH) of the E-protein family, proven to play an important role in developmental processes like neurogenesis, mesoderm formation, and cranial vault development. In humans, mutations in TCF12 lead to craniosynostosis, a congenital birth disorder characterized by the premature fusion of one or several of the cranial sutures. Current research has been primarily focused on functional studies of TCF12, hence the cellular expression profile of this gene during embryonic development and early stages of ossification remains poorly understood. Here we present the establishment and detailed analysis of two transgenic tcf12:EGFP fluorescent zebrafish (Danio rerio) reporter lines. Using these transgenic lines, we analyzed the general spatiotemporal expression pattern of tcf12 during different developmental stages and put emphasis on skeletal development and cranial suture patterning. We identified robust tcf12 promoter-driven EGFP expression in the central nervous system (CNS), the heart, the pronephros, and the somites of zebrafish embryos. Additionally, expression was observed inside the muscles and bones of the viscerocranium in juvenile and adult fish. During cranial vault development, the transgenic fish show a high amount of tcf12 expressing cells at the growth fronts of the ossifying frontal and parietal bones and inside the emerging cranial sutures. Subsequently, we tested the transcriptional activity of three evolutionary conserved non-coding elements (CNEs) located in the tcf12 locus by transient transgenic assays and compared their in vivo activity to the expression pattern determined in the transgenic tcf12:EGFP lines. We could validate two of them as tcf12 enhancer elements driving specific gene expression in the CNS during embryogenesis. Our newly established transgenic lines enhance the understanding of tcf12 gene regulation and open up the possibilities for further functional investigation of these novel tcf12 enhancer elements in zebrafish.