FoxO6 regulates Hippo signaling and growth of the craniofacial complex.

The mechanisms that regulate post-natal growth of the craniofacial complex and that ultimately determine the size and shape of our faces are not well understood. Hippo signaling is a general mechanism to control tissue growth and organ size, and although it is known that Hippo signaling functions in neural crest specification and patterning during embryogenesis and before birth, its specific role in postnatal craniofacial growth remains elusive. We have identified the transcription factor FoxO6 as an activator of Hippo signaling regulating neonatal growth of the face. During late stages of mouse development, FoxO6 is expressed specifically in craniofacial tissues and FoxO6-/- mice undergo expansion of the face, frontal cortex, olfactory component and skull. Enlargement of the mandible and maxilla and lengthening of the incisors in FoxO6-/- mice are associated with increases in cell proliferation. In vitro and in vivo studies demonstrated that FoxO6 activates Lats1 expression, thereby increasing Yap phosphorylation and activation of Hippo signaling. FoxO6-/- mice have significantly reduced Hippo Signaling caused by a decrease in Lats1 expression and decreases in Shh and Runx2 expression, suggesting that Shh and Runx2 are also linked to Hippo signaling. In vitro, FoxO6 activates Hippo reporter constructs and regulates cell proliferation. Furthermore PITX2, a regulator of Hippo signaling is associated with Axenfeld-Rieger Syndrome causing a flattened midface and we show that PITX2 activates FoxO6 expression. Craniofacial specific expression of FoxO6 postnatally regulates Hippo signaling and cell proliferation. Together, these results identify a FoxO6-Hippo regulatory pathway that controls skull growth, odontogenesis and face morphology.

Childhood body mass index is associated with early dental development and eruption in a longitudinal sample from the Iowa Facial Growth Study.

INTRODUCTION: Children with high body mass index (BMI) values have been demonstrated to have precocious dental development. Research has largely focused on cross-sectional data sets, leaving an incomplete understanding of the longitudinal relationship between BMI and dental maturation. METHODS: We used a pure longitudinal growth series to examine the relationship between dental development and childhood BMI. Periapical radiographs from 77 children from the Iowa Growth Study were used to estimate dental development for those with high BMI values. RESULTS: We confirmed prior studies in finding that children with higher BMI values were more likely to have advanced dental development for their ages (P <0.001). BMI at age 4 years was predictive for the timing of dental development at age 12 (P = 0.052). The precocity of the rate of dental development accelerated across growth. Overall dental development scores also correlated with the age of dental eruption for the mandibular canines and first premolars (P <0.001). CONCLUSIONS: High BMI values at young ages predict advanced dental development at later times, suggesting a long-term effect of BMI on dental maturation and implying the need for earlier orthodontic interventions in obese children. These results corroborate those of previous studies, building further evidence that relatively early dental eruption is another consequence of childhood obesity.

Long-term skeletal effects of high-pull headgear followed by fixed appliances for the treatment of Class II malocclusions.

OBJECTIVES: The long-term skeletal effects of Class II treatment in growing individuals using high-pull facebow headgear and fixed edgewise appliances have not been reported. The purpose of this study was to evaluate the long-term skeletal effects of treatment using high-pull headgear followed by fixed orthodontic appliances compared to an untreated control group. MATERIALS AND METHODS: Changes in anteroposterior and vertical cephalometric measurements of 42 Class II subjects (n = 21, mean age = 10.7 years) before treatment, after headgear correction to Class I molar relationship, after treatment with fixed appliances, and after long-term retention (mean 4.1 years), were compared to similar changes in a matched control group (n = 21, mean age = 10.9 years) by multivariable linear regression models. RESULTS: Compared to control, the study group displayed significant long-term horizontal restriction of A-point (SNA = -1.925°, P < .0001; FH-NA = -3.042°, P < .0001; linear measurement A-point to Vertical Reference = -3.859 mm, P < .0001) and reduction of the ANB angle (-1.767°, P < .0001), with no effect on mandibular horizontal growth or maxillary and mandibular vertical skeletal changes. A-point horizontal restriction and forward mandibular horizontal growth accompanied the study group correction to Class I molar, and these changes were stable long term. CONCLUSIONS: One phase treatment for Class II malocclusion with high-pull headgear followed by fixed orthodontic appliances resulted in correction to Class I molar through restriction of horizontal maxillary growth with continued horizontal mandibular growth and vertical skeletal changes unaffected. The anteroposterior molar correction and skeletal effects of this treatment were stable long term.

Integration of the nasal complex: Implications for developmental and evolutionary change in modern humans.

OBJECTIVES: Assessing the strength of integration among different regions of the modern human nasal complex is important for developing a more thorough understanding of the determinants of nasal morphology. Given the morphogenetic influence of cartilage on adjacent intramembranous growth sites, the interaction between chondrocranial- versus intramembranous-derived nasal structures may have a significant influence on patterns of nasal variation. The purpose of this study is to examine integration between the chondrocranial- and intramembranous-derived regions of the nasal complex. MATERIALS AND METHODS: Using computed tomograph (CT) scans, we collected three-dimensional coordinate landmark data from a static adult sample (n = 62). First, using centroid size, and the symmetric and asymmetric components of shape variation, we examined the strength of integration between landmarks representing chondrocranial-derived structures (e.g., ethmoid, external nasal cartilages) and landmarks representing intramembranous-derived structures (nasal floor, anterior nasal aperture, etc.). Second, given that the strength of integration is a relative measure, we compared integration between chondrocranial- and intramembranous-derived structures to the more modularized external and internal regions of the nasal complex. RESULTS: There was significant moderate morphological integration between chondrocranial- versus intramembranous-derived regions of the nasal complex. Moreover, integration between chondrocranial- versus intramembranous-derived structures was consistently stronger when compared to external versus internal regions for both the symmetric and asymmetric components of variation. Thus, more covariation within the nasal complex could be explained by the relationship between chondrocranial- and intramembranous-derived structures. CONCLUSIONS: Our results suggest that the interaction between chondrocranial- and intramembranous-derived structures may be an important determinant in the patterning of nasal complex variation.

Impact of cone-beam computed tomography scan mode on the diagnostic yield of chemically simulated external root resorption.

INTRODUCTION: The aim of this in-vitro study was to evaluate the influence of cone-beam computed tomography scans on the diagnosis of chemically simulated external root resorption. METHODS: One hundred extracted anterior teeth were selected. Subsurface demineralization was induced on a limited area of the apical third of the root of 49 teeth. Each tooth was placed in an empty socket of a partially edentulous dry mandible. Cone-beam computed tomography images were obtained according to 3 protocols: (1) half scan, 0.40-mm voxel size; (2) full scan, 0.40-mm voxel size; and (3) full scan, 0.125-mm voxel size. Three observers evaluated the images. Sensitivity, specificity, accuracy, and area under the curve were compared with the Cochran Q and Mann-Whitney U tests. RESULTS: Protocol 3 had the highest sensitivity (81.63%), accuracy (80.67%), and area under the curve (0.807). There were statistically significant differences between protocol 3 and the other 2 protocols (P <0.001). The specificity of protocol 1 (84.97%) was greater than that of protocols 2 (69.93%) and 3 (79.74%); however, a statistically significant difference was found only between protocols 1 and 2 (P = 0.005). CONCLUSIONS: A more dedicated, high-resolution scan should be acquired when one intends to investigate the early stage of external root resorption during orthodontic treatment. However, this does not imply that all orthodontic patients should be subjected to high-dose cone-beam computed tomography scans.

Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping.

Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx) arrays to enable directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the Prdm16 transcription factor gene. We demonstrate that the gene trap insertion creates a null mutation replicating the Pierre Robin sequence-type cleft palate phenotype of other Prdm16 mutant mice. Consecutive breeding to Flpe and Emx1IREScre deleter mice spatially restricted Prdm16 loss to regions of the forebrain expressing the homeobox gene Emx1, demonstrating the utility of the technology for the analysis of tissue-specific gene functions.

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion.

INTRODUCTION: Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. METHODS: Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. RESULTS: Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P < 0.05) were identified with PITX2, SNAI3, 11q22.2-q22.3, 4p16.1, ISL1, and FGF8. Principal component analysis for asymmetric variations identified 4 components that explained 51% of the total variations and captured left-to-right discrepancies resulting in midline deviations, unilateral crossbites, and ectopic eruptions. Suggestive associations were found with TBX1AJUBA, SNAI3SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P <0.00022). Suggestive associations were found for centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. CONCLUSIONS: Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified.

Morphological interaction between the nasal septum and nasofacial skeleton during human ontogeny.

The nasal septal cartilage is thought to be a key growth center that contributes to nasofacial skeletal development. Despite the developmental influence of the nasal septum however, humans often exhibit a high frequency of septal deviation suggesting discordance in the growth between the septum and surrounding nasofacial skeleton. While there are numerous etiological factors that contribute to septal deviation, the surrounding nasofacial skeleton may also act to constrain the septum, resulting in altered patterns of growth. That is, while the nasal septum has a direct morphogenetic influence on aspects of the nasofacial skeleton, other nasofacial skeletal components may restrict septal growth resulting in deviation. Detailing the developmental relationship between these structures is important not only for understanding the causal determinants of nasal septal deviation, but also for developing a broader understanding of the complex interaction between the facial skeleton and chondrocranium. We selected 66 non-syndromic subjects from the University of Minnesota Orthodontic Clinic who ranged from 7 to 18 years in age and had an existing pretreatment cone-beam computed tomography (CBCT) scan. Using CBCT data, we examined the developmental relationship between nasal septal deviation and the surrounding nasofacial skeleton. We measured septal deviation as a percentage of septal volume relative to a modeled non-deviated septum. We then collected a series of coordinate landmark data in the region immediately surrounding the nasal septum in the midsagittal plane representing the nasofacial skeleton. First, we examined ontogenetic changes in the magnitude of nasal septal deviation relative to chronological age and nasofacial size. Next, using Procrustes-based geometric morphometric techniques, we assessed the morphological relationship between nasal septal deviation and nasofacial skeletal shape. Our results indicate that variation in the magnitude of nasal septal deviation was established in our earliest age group and maintained throughout ontogeny. Moreover, nasal septal deviation was correlated with non-allometric variation in nasofacial shape restricted to the region of the anterior sphenoid body. Ultimately, our results suggest that early developmental variation in midline basicranial components may act to alter or constrain patterns of nasal septal growth.

Betwixt and Between: Intracranial Perspective on Zygomatic Arch Plasticity and Function in Mammals.

The zygomatic arch is morphologically complex, providing a key interface between the viscerocranium and neurocranium. It also serves as an attachment site for masticatory muscles, thereby linking it to the feeding apparatus. Though morphological variation related to differential loading is well known for many craniomandibular elements, the adaptive osteogenic response of the zygomatic arch remains to be investigated. Here, experimental data are presented that address the naturalistic influence of masticatory loading on the postweaning development of the zygoma and other cranial elements. Given the similarity of bone-strain levels among the zygoma and maxillomandibular elements, a rabbit and pig model were used to test the hypothesis that variation in cortical bone formation and biomineralization along the zygomatic arch and masticatory structures are linked to increased stresses. It was also hypothesized that neurocranial structures would be minimally affected by varying loads. Rabbits and pigs were raised for 48 weeks and 8 weeks, respectively. In both experimental models, CT analyses indicated that elevated masticatory loading did not induce differences in cortical bone thickness of the zygomatic arch, though biomineralization was positively affected. Hypotheses were supported regarding bone formation for maxillomandibular and neurocranial elements. Varying osteogenic responses in the arch suggests that skeletal adaptation, and corresponding variation in performance, may reside differentially at one level of bony architecture. Thus, it is possible that phenotypic diversity in the mammalian zygoma is due more singularly to natural selection (vs. plasticity). These findings underscore the complexity of the zygomatic arch and, more generally, determinants of skull form. Anat Rec, 299:1646-1660, 2016. © 2016 Wiley Periodicals, Inc.

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal.

Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation. Tamoxifen-induced inactivation of Sox2 demonstrates the requirement of Sox2 for maintenance of the DESCs in adult mice. Conditional overexpression of Lef-1 in mice increases DESC proliferation and creates a new labial cervical loop stem cell compartment, which produces rapidly growing long tusk-like incisors, and Lef-1 epithelial overexpression partially rescues the tooth arrest in Sox2 conditional knockout mice. Mechanistically, Pitx2 and Sox2 interact physically and regulate Lef-1, Pitx2 and Sox2 expression during development. Thus, we have uncovered a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates DESC homeostasis and dental development.

Spatial determinants of the mandibular curve of Spee in modern and archaic Homo.

OBJECTIVES: The curve of Spee (COS) is a mesio-distally curved alignment of the canine through distal molar cusp tips in certain mammals including modern humans and some fossil hominins. In humans, the alignment varies from concave to flat, and previous studies have suggested that this difference reflects craniofacial morphology, including the degree of alveolar prognathism. However, the relationship between prognathism and concavity of the COS has not been tested in craniofacially variant populations. We tested the hypothesis that greater alveolar prognathism covaries with a flatter COS in African-American and European-American populations. We further examined this relationship in fossil Homo including Homo neanderthalensis and early anatomically modern Homo sapiens, which are expected to extend the amount of variation in the COS from the extant sample. METHODS AND MATERIALS: These hypotheses were tested using three-dimensional geometric morphometrics. Landmarks were recorded from the skulls of 166 African-Americans, 123 European-Americans, and 10 fossil hominin mandible casts. Landmarks were subjected to generalized Procrustes analysis, principal components analysis, and two-block partial least squares analysis. RESULTS: We documented covariation between the COS and alveolar prognathism such that relatively prognathic individuals have a flatter COS. Mandibular data from the fossil hominin taxa generally confirm and extend this correlation across a greater range of facial size and morphology in Homo. DISCUSSION: Our results suggest that the magnitude of the COS is related to a suite of features associated with alveolar prognathism in modern humans and across anthropoids. We also discuss the implications for spatial interactions between the dental arches.

Variation in the Developmental and Morphological Interaction Between the Nasal Septum and Facial Skeleton.

While the nasal septum exerts a morphogenetic influence on the facial skeleton, there is evidence that this relationship is highly variable. To better appreciate the precise role of the septum, it is important understand the variable interaction between the septum and surrounding skeleton during ontogeny. Here we analyzed nasal septal and facial skeletal postnatal phenotypic variation using cross-sectional samples of C3H/HeJ and C57BL/6J mice. Initial observations indicated between-strain variation in the magnitude of septal deviation, suggesting differences in septal and facial skeletal interaction. We examined whether variation in septal deviation is due to ontogenetic differences in septal size, or whether variation in facial skeletal growth imposes spatial constraints on the septum. Using microCT we quantified septal size and deviation, and collected coordinate landmark data, which we analyzed using geometric morphometrics. C3H/HeJ mice were significantly more deviated than C57BL/6J during development. We found no differences in septal size between the two strains. However, while both strains exhibited an ontogenetic increase in snout length, C3H/HeJ mice exhibited a non-allometric reduction in nasal bone length. This appears to be influenced by between-strain variation in the spatial relationship between the nasal septum and nasofrontal suture. Unlike C57BL/6J mice, the C3H/HeJ nasal septum is positioned anterior to the nasofrontal suture potentially limiting an early direct influence of septal growth (e.g., through interstitial expansion) on sutural growth. Ultimately, our results underscore that while the septum is a key facial growth center, its precise influence on facial growth varies even in narrow morphological and taxonomic ranges. Anat Rec, 299:730-740, 2016. © 2016 Wiley Periodicals, Inc.

The ontogeny of nasal shape: An analysis of sexual dimorphism in a longitudinal sample.

OBJECTIVES: Potential integration between the nasal region and noncranial components of the respiratory system has significant implications for understanding determinants of craniofacial variation. There is increasing evidence that sexual dimorphism in body size and associated male-female differences in energetically relevant variables influence the development of the nasal region. To better understand this relationship, we examined the ontogeny of sexual dimorphism in nasal shape using a longitudinal series of lateral cephalograms. METHODS: We collected a series of two dimensional coordinate landmark data from n = 20 males and n = 18 females from 3.0 to 20.0+ years of age totaling n = 290 observations across nine age groups. First, we tested whether there are sex differences in the nasal shape related to ontogenetic increases in body size (i.e., sitting height). Additionally, we examined whether there are male-female differences in patterns of nonallometric variation in nasal shape. Next, we tested whether there are sex differences in the strength of integration between the nasal region and other aspects of the facial skeleton. RESULTS: Our results indicate that there are a number of similarities in patterns of morphological variation in the nasal region between males and females. However, as sitting height increases males exhibit a disproportionate increase in nasal region height that is not present in the female sample. Moreover, the male nasal region is less integrated with the surrounding facial skeleton when compared to the female sample. CONCLUSIONS: These results are consistent with the hypothesis that sex differences in nasal development are associated with male-female differences in energetically relevant variables.

Nasal Septal Deviation and Facial Skeletal Asymmetries.

During ontogeny, the nasal septum exerts a morphogenetic influence on the surrounding facial skeleton. While the influence of the septum is well established in long snouted animal models, its role in human facial growth is less clear. If the septum is a facial growth center in humans, we would predict that deviated septal growth would be associated with facial skeletal asymmetries. Using computed tomographic (CT) scans of n = 55 adult subjects, the purpose of this study was to test whether there is a correlation between septal deviation and facial asymmetries using three-dimensional (3D) geometric morphometric techniques. We calculated deviation as a percentage of septal volume relative to the volume of a modeled non-deviated septum. We then recorded skeletal landmarks representing the nasal, palatal, and lateral facial regions. Landmark data were superimposed using Procrustes analysis. First, we examined the correlation between nasal septal deviation and the overall magnitude of asymmetry. Next, we assessed whether there was a relationship between nasal septal deviation and more localized aspects of asymmetry using multivariate regression analysis. Our results indicate that while there was no correlation between septal deviation and the overall magnitude of asymmetry, septal deviation was associated with asymmetry primarily in the nasal floor and the palatal region. Septal deviation was unassociated with asymmetries in the lateral facial skeleton. Though we did not test the causal relationship between nasal septal deviation and facial asymmetry, our results suggest that the nasal septum may have an influence on patterns of adult facial form.

The effects of altered maxillary growth on patterns of mandibular rotation in a pig model.

OBJECTIVES: A thorough understanding of influence of maxillary growth on patterns of mandibular rotation during development is important with regard to the treatment of skeletal discrepancies. In the present study, we examined whether experimentally altered maxillary position has a significant influence on patterns of mandibular rotation in a pig model. DESIGN: Maxillary growth was altered in a sample of n=10 domestic pigs via surgical fixation of the circummaxillary sutures. We compared the experimental group to control and surgical sham samples and assessed the effects of altered maxillary growth on mandibular form using geometric morphometric techniques. We tested for significant differences in mandibular shape between our samples and examined axes of morphological variation. Additionally, we examined whether altered mandibular shape resulting from altered maxillary position was predictably associated with morphological changes to the condylar region. RESULTS: There was a statistically significant difference in mandibular shape between the experimental and control/sham groups. As a result of vertical displacement of the snout, mandibles in the experimental sample resulted in greater anterior rotation when compared to the control/sham pigs. Variation in rotation was correlated with morphological changes in the condyle including the shape of the articular surface and condylar orientation indicative of greater anterior mandibular rotation. CONCLUSIONS: Vertical displacement of the maxilla had a significant effect on mandibular shape by encouraging anterior mandibular rotation. This result has important implications for understanding the effects of altered mandibular posture on condylar remodeling the treatment of skeletal discrepancies such as the correction of hyperdivegent mandibular growth.

Functional and morphological correlates of mandibular symphyseal form in a living human sample.

Variation in recent human mandibular form is often thought to reflect differences in masticatory behavior associated with variation in food preparation and subsistence strategies. Nevertheless, while mandibular variation in some human comparisons appear to reflect differences in functional loading, other comparisons indicate that this relationship is not universal. This suggests that morphological variation in the mandible is influenced by other factors that may obscure the effects of loading on mandibular form. It is likely that highly strained mandibular regions, including the corpus, are influenced by well-established patterns of lower facial skeletal integration. As such, it is unclear to what degree mandibular form reflects localized stresses incurred during mastication vs. a larger set of correlated features that may influence bone distribution patterns. In this study, we examine the relationship between mandibular symphyseal bone distribution (i.e., second moments of area, cortical bone area) and masticatory force production (i.e., in vivo maximal bite force magnitude and estimated symphyseal bending forces) along with lower facial shape variation in a sample of n = 20 living human male subjects. Our results indicate that while some aspects of symphyseal form (e.g., wishboning resistance) are significantly correlated with estimates of symphyseal bending force magnitude, others (i.e., vertical bending resistance) are more closely tied to variation in lower facial shape. This suggests that while the symphysis reflects variation in some variables related to functional loading, the complex and multifactorial influences on symphyseal form underscores the importance of exercising caution when inferring function from the mandible especially in narrow taxonomic comparisons.

Ontogenetic scaling of the human nose in a longitudinal sample: implications for genus Homo facial evolution.

Researchers have hypothesized that nasal morphology, both in archaic Homo and in recent humans, is influenced by body mass and associated oxygen consumption demands required for tissue maintenance. Similarly, recent studies of the adult human nasal region have documented key differences in nasal form between males and females that are potentially linked to sexual dimorphism in body size, composition, and energetics. To better understand this potential developmental and functional dynamic, we first assessed sexual dimorphism in the nasal cavity in recent humans to determine when during ontogeny male-female differences in nasal cavity size appear. Next, we assessed whether there are significant differences in nasal/body size scaling relationships in males and females during ontogeny. Using a mixed longitudinal sample we collected cephalometric and anthropometric measurements from n = 20 males and n = 18 females from 3.0 to 20.0+ years of age totaling n = 290 observations. We found that males and females exhibit similar nasal size values early in ontogeny and that sexual dimorphism in nasal size appears during adolescence. Moreover, when scaled to body size, males exhibit greater positive allometry in nasal size compared to females. This differs from patterns of sexual dimorphism in overall facial size, which are already present in our earliest age groups. Sexually dimorphic differences in nasal development and scaling mirror patterns of ontogenetic variation in variables associated with oxygen consumption and tissue maintenance. This underscores the importance of considering broader systemic factors in craniofacial development and may have important implications for the study of patters craniofacial evolution in the genus Homo.

The morphological interaction between the nasal cavity and maxillary sinuses in living humans.

To understand how variation in nasal architecture accommodates the need for effective conditioning of respired air, it is necessary to assess the morphological interaction between the nasal cavity and other aspects of the nasofacial skeleton. Previous studies indicate that the maxillary sinuses may play a key role in accommodating climatically induced nasal variation such that a decrease in nasal cavity volume is associated with a concomitant increase in maxillary sinus volume. However, due to conflicting results in previous studies, the precise interaction of the nasal cavity and maxillary sinuses, in humans, is unclear. This is likely due to the prior emphasis on nasal cavity size, whereas arguably, nasal cavity shape is more important with regard to the interaction with the maxillary sinuses. Using computed tomography scans of living human subjects (N=40), the goal of this study is to assess the interaction between nasal cavity form and maxillary sinus volume in European- and African-derived individuals with differences in nasal cavity morphology. First, we assessed whether there is an inverse relationship between nasal cavity and maxillary sinus volumes. Next, we examined the relationship between maxillary sinus volume and nasal cavity shape using multivariate regression. Our results show that there is a positive relationship between nasal cavity and maxillary sinus volume, indicating that the maxillary sinuses do not accommodate variation in nasal cavity size. However, maxillary sinus volume is significantly correlated with variation in relative internal nasal breadth. Thus, the maxillary sinuses appear to be important for accommodating nasal cavity shape rather than size.

Nasal septal and craniofacial form in European- and African-derived populations.

As a component of the chondrocranium, the nasal septum influences the anteroposterior dimensions of the facial skeleton. The role of the septum as a facial growth center, however, has been studied primarily in long-snouted mammals, and its precise influence on human facial growth is not as well understood. Whereas the nasal septum may be important in the anterior growth of the human facial skeleton early in ontogeny, the high incidence of nasal septal deviation in humans suggests the septum's influence on human facial length is limited to the early phases of facial growth. Nevertheless, the nasal septum follows a growth trajectory similar to the facial skeleton and, as such, its prolonged period of growth may influence other aspects of facial development. Using computed tomography scans of living human subjects (n = 70), the goal of the present study is to assess the morphological relationship between the nasal septum and facial skeleton in European- and African-derived populations, which have been shown to exhibit early developmental differences in the nasal septal-premaxillary complex. First we assessed whether there is population variation in the size of the nasal septum in European- and African-derived samples. This included an evaluation of septal deviation and the spatial constraints that influence variation in this condition. Next, we assessed the relationship between nasal septal size and craniofacial shape using multivariate regression techniques. Our results indicate that there is significant population variation in septal size and magnitude of septal deviation, both of which are greater in the European-derived sample. While septal deviation suggests a disjunction between the nasal septum and other components of the facial skeleton, we nevertheless found a significant relationship between the size of the nasal septum and craniofacial shape, which appears to largely be a response to the need to accommodate variation in nasal septal size.