Studies on orthocephalization. 10. Behaviour of the visceral part of the rat head during the first 14 days after gestation

The present paper considers the significance of interosseous flexions of the palatal complex in the process of orthocephalization of the rat skull between birth and 7 d p.n. The study is based on a sample of 90 rats divided into 4 age groups, i.e. 0, 4, 7, and 14 d. These rats have been X-rayed, and their photographs subsequently analysed. During the studied period, the constituents of the bony palate, i.e. the horizontal part of the palatine bone, the palatal process of maxilla and the palatal part of premaxilla, increase markedly in length, but with individual differences in growth rate. There is, in the period, a marked decrease in angulation between the cranial base and the palatal plane. This means that the rat skull becomes more orthocranial. There is also a straightening (orthopalatalization) of the palate, as the angle between maxilla and premaxilla becomes more obtuse, and a marked decrease in angulation between the palatine bone and the cranial base. The patterns of angular changes suggest that the process of orthocephalization in the period between birth and 14 d p.n. primarily is a result of an upwards rotation of the palatine bone relative to the cranial base, while interosseous deflections in the palate only play a minor role.     

Studies on orthocephalization. 2. Flexions of the rat head in the period between 14 and 60 days after gestation

The present paper considers the significance of a variety of cranial flexions in the process of orthocephalization of the rat skull between 14 and 60 days postnatally. The study is based on a sample of 27 male rats, who have been x-rayed at 14, 30 and 60 days with subsequent analyses of the photographs obtained. In this period the angle between the cranial base and the facial part of the skull becomes more obtuse, i.e. the skull becomes more orthocranial. The cranial base becomes at the same time more airobasal (lordotic). Angular changes between the individual bones in the cranial vault straightens the vault markedly. By this it becomes orthodorsal. As the angle between the basisphenoid and the parietal bones stays more or less constant between 14 and 60 days, the impression is created that both the anterior and posterior parts of the neural skull rotate upwards relative to this bone complex. Thus, orthocephalization in the period between 14 and 60 days both consists of flexions between the facial and neural parts of the skull (prebasal flexions), and may be more importantly of interosseous ventral and dorsal flexions.     

Facial suture synostosis of newborn Fgfr1(P250R/+) and Fgfr2(S252W/+) mouse models of Pfeiffer and Apert syndromes

Apert and Pfeiffer syndromes are hereditary forms of craniosynostosis characterized by midfacial hypoplasia and malformations of the limbs and skull. A serious consequence of midfacial hypoplasia in these syndromes is respiratory compromise due to airway obstruction. In this study, we have evaluated Fgfr1(P250R/+) and Fgfr2(S252W/+) mouse models of these human conditions to study the pathogenesis of midfacial hypoplasia. Our histologic and micro-CT evaluation revealed premature synostosis of the premaxillary-maxillary, nasal-frontal, and maxillary-palatine sutures of the face and dysplasia of the premaxilla, maxilla, and palatine bones. These midfacial abnormalities were detected in the absence of premature ossification of the cranial base at postnatal day 0. Our results indicate that midfacial hypoplasia is not secondary to premature cranial base ossification but rather primary synostosis of facial sutures. Birth Defects Research (Part A), 2011.     

Human palatal growth evaluated on medieval crania using nerve canal openings as references

The purpose of this investigation was to measure postnatal lengthening and widening of the hard palate by use of nerve canal openings as references. The relationship of the dentition to the greater palatine foramina was also investigated. Thirty-nine medieval dry skulls were examined, 22 from children and 17 from adults. All crania were photographed at a 1:1 scale. The dimensions of the maxilla and the location of the dentition were determined from the photographs. The study showed that palatal growth in length in the sagittal plane takes place anterior to the greater palatine foramen. The growth increment in the area between the incisive foramen and the transverse palatine suture is more pronounced than the growth increment in the area between the transverse palatine suture and the greater palatine foramen. The distance from the greater palatine foramina to the posterior margin of the palate did not increase significantly with age. The growth in width seems to continue into adult life. The first permanent molars and the surrounding bone are moved forwards in relation to the greater palatine foramina during growth. The space for the developing maxillary premolars and molars therefore has to be obtained by growth in the transverse palatine suture. © 1996 Wiley-Liss, Inc.     

Growth status of children treated for unilateral cleft lip and palate

Cephalometric distances, angles, and proportions were evaluated for 32 children 5 to 8 years of age treated for unilateral cleft lip and palate. The children were age and sex matched with untreated controls with normal skeletal relationships. The unilateral cleft lip and palate sample was treated by the same surgeon and orthodontist using the same techniques and appliances. Measures of overall facial proportions, facial convexity, and prognathism were not significantly different between the two groups. The primary group differences pertain to the posterior aspect of the maxilla, which is vertically short in the unilateral cleft lip and palate sample. Horizontally, the maxilla of the unilateral cleft lip and palate children was significantly longer, producing a steeper palatal plane. In addition, the zygoma and orbits of unilateral cleft lip and palate children were somewhat retruded; the posterior cranial base and total mandibular length also were longer in the unilateral cleft lip and palate children.     

Anatomical study of the skull of amphisbaenian Diplometopon zarudnyi (Squamata,Amphisbaenia)

This study investigates the amphisbaenian species skull which includes cranium, lower jaw and hyoid apparatus. The medial dorsal bones comprise the premaxilla, nasal, frontal and parietal. The premaxilla carries a large medial tooth and two lateral ones. The nasals are paired bones and separated by longitudinal suture. Bones of circumorbital series are frontal, orbitosphenoid and maxilla. The occipital ring consists of basioccipital, supraoccipital and exooccipital. Supraoccipital and basioccipital are single bones while the exo-occipitals are paired. The bones of the palate comprise premaxilla, maxilla, septomaxilla, palatine, pterygoid, ectopterygoid, basisphenoid, parasphenoid, orbitosphenoid and laterosphenoid. Prevomer and pterygoid teeth are absent. Palatine represent by two separate bones. The temporal bones are clearly visible. The lower jaw consists of the dentary, articular, coronoid, supra-angular, angular and splenial. The hyoid apparatus is represented by a Y-shaped structure. The mandible is long and is suspended from the braincase via relatively short quadrate. There is an extensive contact between the long angular and the large triangular coronoid. Thus inter-mandibular joint is bridged completely by the angular and consequently, the lower jaws are relatively rigid and kinetic. The maxillae are suspended from the braincase largely by ligaments and muscles rather than through bony articulation. In conclusion, the skull shape affects feeding strategy in Diplometopon zarudnyi. The prey is ingested and transported via a rapid maxillary raking mechanism.     

Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation

Cleft palate, including submucous cleft palate, is among the most common birth defects in humans. While overt cleft palate results from defects in growth or fusion of the developing palatal shelves, submucous cleft palate is characterized by defects in palatal bones. In this report, we show that the Bmpr1a gene, encoding a type I receptor for bone morphogenetic proteins (Bmp), is preferentially expressed in the primary palate and anterior secondary palate during palatal outgrowth. Following palatal fusion, Bmpr1a mRNA expression was upregulated in the condensed mesenchyme progenitors of palatal bone. Tissue-specific inactivation of Bmpr1a in the developing palatal mesenchyme in mice caused reduced cell proliferation in the primary and anterior secondary palate, resulting in partial cleft of the anterior palate at birth. Expression of Msx1 and Fgf10 was downregulated in the anterior palate mesenchyme and expression of Shh was downregulated in the anterior palatal epithelium in the Bmpr1a conditional mutant embryos, indicating that Bmp signaling regulates mesenchymal-epithelial interactions during palatal outgrowth. In addition, formation of the palatal processes of the maxilla was blocked while formation of the palatal processes of the palatine was significantly delayed, resulting in submucous cleft of the hard palate in the mutant mice. Our data indicate that Bmp signaling plays critical roles in the regulation of palatal mesenchyme condensation and osteoblast differentiation during palatal bone formation.     

Spontaneous complete clefting of the palates in a mouse fetus: a study by scanning electron microscopy and serial section reconstruction

A 15 day mouse fetus having spontaneous complete clefting of the primary and secondary palates was studied in comparison with its normal litter mates and with normal 14 day fetuses. Specimens were studied by scanning electron microscopy at various stages of microdissection, by light microscopy of thin serial sections and by serial section reconstruction of the anterior chondrocranium of the clefted specimen and one of its normal litter mates. Differentiation of tooth and bone tissue was slightly retarded in the clefted fetus but paranasal and oral landmarks, though distorted, were present. The clefted fetus had a smaller angle between cranial base and nasal capsule and a marked discontinuity between the primary and secondary palates. Cell surfaces on the medial edge of the secondary palate in the clefted fetus resembled cell surfaces of oral areas that do not normally fuse, i.e. they are polygonial, flat and bear few surface projections in contrast to the normal 14 day condition where these cells are spindle shaped, convex and have many microvilli. The observations support the concepts that clefting of the secondary palate is consequential to clefting of the primary palate, that maldevelopment of neural crest mesenchyme is not necessarily a contributing factor, that clefting of the primary and secondary palates is associated with a shorter anterior-posterior dimension of the head and that when fusion of palatal shelves fails to occur the cells of the medial edges modulate in the direction of a generalized type of surface epithelium.     

Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects

Cleft palate and skull malformations represent some of the most frequent congenital birth defects in the human population. Previous studies have shown that TGFbeta signaling regulates the fate of the medial edge epithelium during palatal fusion and postnatal cranial suture closure during skull development. It is not understood, however, what the functional significance of TGFbeta signaling is in regulating the fate of cranial neural crest (CNC) cells during craniofacial development. We show that mice with Tgfbr2 conditional gene ablation in the CNC have complete cleft secondary palate, calvaria agenesis, and other skull defects with complete phenotype penetrance. Significantly, disruption of the TGFbeta signaling does not adversely affect CNC migration. Cleft palate in Tgfbr2 mutant mice results from a cell proliferation defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Our data suggests that TGFbeta IIR plays a crucial, cell-autonomous role in regulating the fate of CNC cells during palatogenesis. During skull development, disruption of TGFbeta signaling in the CNC severely impairs cell proliferation in the dura mater, consequently resulting in calvaria agenesis. We provide in vivo evidence that TGFbeta signaling within the CNC-derived dura mater provides essential inductive instruction for both the CNC- and mesoderm-derived calvarial bone development. This study demonstrates that TGFbeta IIR plays an essential role in the development of the CNC and provides a model for the study of abnormal CNC development.     

Sutural expansion osteogenesis for management of the bony-tissue defect in cleft palate repair: experimental studies in dogs

A series of experimental studies on sutural expansion osteogenesis for management of the bony-tissue defect in cleft palate repair was performed between 1995 and 1997. Forty-five young dogs in weaning were used in four experiments that were divided into two parts. Part I probed the possibility of closing the surgically constructed hard palate cleft not only with mucoperiosteum but also with bony tissue by the technique of sutural expansion of lateral palatine sutures. Part II explored the possibility of pushing the palatine bone posteriorly and advancing the maxillary segment anteriorly by transverse palatine suture expansion. In Part I, a ring-shaped suture expander made of nickel-titanium shape memory alloy was used to expand the lateral suture of palatine bones. Expansion forces of 200 G, 360 G, and 480 G were used for the first experiment. A force of 360 G was chosen for two other experiments; this force is equivalent to the distraction rate of 0.5 mm per day of a jackscrew device. The ring-shaped suture expander was opened and its two feet were fixed in the medial sides of residual horizontal plates of the palatine bones immediately after a hard palate cleft was constructed surgically under endotracheal general anesthesia. At the eighth postoperative day, under the traction of 360 G, the two sides of the 8-mm-wide hard palate cleft were brought into contact with each other, and 8 or 9 days later the closed palatal cleft had healed completely with mucosal tissue. This experiment was repeated twice and yielded the same results. Sutural expansion osteogenesis was evaluated physically, fluorescently, histologically, and ultrastructurally to examine the deposition of the regenerated bone in the suture areas. Additionally, the influence of sutural expansion osteogenesis of the palatal bones on other facial bones was also studied cephalometrically. In Part II, a bow-shaped suture expander made of nickel-titanium shape memory alloy was applied to expand either the left or the right side of the transverse palatal suture of each of the experimental dogs. At the postoperative week 4 to 6, the maxillary segment was moved forward 5 to 6 mm on the expanded side, and the palatal bone was pushed backward 5 mm. The changes of bone position were assessed radiographically and cephalometrically. Tissue response of circum-maxillary sutures was examined histologically. These experiments led to the following conclusions: (1) Bony closure of the surgically constructed hard palate cleft with a ring-shaped suture expander made of nickel-titanium shape memory alloy is possible. (2) Anterior advancement of the maxillary segment and posterior lengthening of the hard palate using a bow-shaped suture expander made of nickel-titanium shape memory alloy applied at the palatomaxillary suture (transverse palatal suture) of the hard palate are also possible. Thus, in humans, a new approach for cleft palate repair may be a worthwhile investigation.     

Evolution of the therian face through complete loss of the premaxilla

The anatomical framework of the jawbones is highly conserved among most of the Osteichthyes, including the tetrapods. However, our recent study suggested that the premaxilla, the rostralmost upper jaw bone, was rearranged during the evolution of therian mammals, being replaced by the septomaxilla at least in the lateral part. In the present study, to understand more about the process of evolution from the ancestral upper jaw to the therian face, we re-examined the development of the therian premaxilla (incisive bone). By comparing mouse, bat, goat, and cattle fetuses, we confirmed that the therian premaxilla has dual developmental origins, the lateral body and the palatine process. This dual development is widely conserved among the therian mammals. Cell-lineage-tracing experiments using Dlx1-CreER^T2 mice revealed that the palatine process arises in the ventral part of the premandibular domain, where the nasopalatine nerve distributes, whereas the lateral body develops from the maxillary prominence in the domain of the maxillary nerve. Through comparative analysis using various tetrapods, we concluded that the palatine process should not be considered part of the ancestral premaxilla. It rather corresponds to the anterior region of the vomerine bone of nonmammalian tetrapods. Thus, the present findings indicate that the true premaxilla was completely lost during the evolution of the therian mammals, resulting in the establishment of the unique therian face as an evolutionary novelty. Reconsideration of the homological framework of the cranial skeleton based on the topographical relationships of the ossification center during embryonic development is warranted.     

Cranial base and jaw relationship

The lateral skull radiographs of 124 boys aged approximately 10 years divided equally between the four angle classes were digitized in an effort to establish the relationship between cranial base size and shape and jaw relationship. Comparison of the means for occlusal groups showed a trend from class II to class III as cranial base dimensions and angle decreased. The condyle was also more distally positioned with respect to nasion, point A and the Pterygomaxillary vertical in the class II groups. Cranial base length correlated strongly with maxillary length but weakly with mandibular length. Nevertheless, the size of the maxilla did not influence its prognathism. The cranial base angle was strongly correlated (-0.7) with angle sella-nasion-point B. It is concluded that cranial base size and shape influence mandibular prognathism by determining the anteroposterior position of the condyle relative to the facial profile.     

Mechanical factors in the evolution of the mammalian secondary palate: a theoretical analysis

The secondary palate of mammals is a bony shelf that closes the ventral aspect of the rostrum. The rostrum, therefore, approximates to a tapered semicylindrical tube that is theoretically a mechanically efficient structure for resisting the forces of biting, including the more prolonged bouts of mastication typical of mammals. Certain mammal-like reptiles illustrate stages in the development of the palate in which the shelves projecting medially from each premaxilla and maxilla do not meet in the midline. We evaluate several geometric properties of sections through the rostrum of the American opossum (Didelphis virginiana). For loading at the incisors and canines, these properties indicate the structural strength and stiffness in both bending and torsion of the rostrum and of single maxillae. We then repeat the analysis but progressively omit segments of the palatal shelf, a procedure which simulates, in reverse, the evolutionary development of the structure. The results demonstrate that the secondary palate contributes significantly to the torsional strength and stiffness of the rostrum of Didelphis and to the strength of each maxilla in lateromedial bending. The major evolutionary implications of the results are that the rapid increase in rostral strength with small increments of the palatal shelves may have been a significant factor in the development of the complete structure. The results indicate that there was a marked jump in torsional strength and stiffness when the shelves met in the midline, which is likely to have been important in the subsequent development of the diverse masticatory mechanisms of cynodonts and mammals. On the basis of this analysis the mammalian secondary palate may be interpreted as one of a number of methods, seen in the mammal-like reptiles, for strengthening the rostrum.     

The anterior half of mouse palatal shelf is elevated by a remodeling movement

During the development of the mammalian secondary palate, the lateral palatine process (the palatal shelf) rises from the vertical plane beside the tongue to the horizontal plane above it. To determine the mode of elevation of the palatal shelf, we have cultured the whole ICR mouse fetus on day 14 (0-2 h) of gestation with a scratch as a marker at the distal edge of the anterior fourth of the vertical palatal shelf. After 6-18 h of culture, the survival ratio was 78.9%, and the palatal shelf rose horizontally above the tongue in 22.2% of the surviving fetuses. The scratch was found as a scar on the oral epithelium laterally to the medial edge of the elevated palatal shelf. These results indicate that the medial edge of the horizontal shelf was newly formed from the medial wall of the preceding vertical-stage shelf during elevation, and that the palatal shelf was elevated by a remodeling process in the anterior half of the shelf.     

Palatal thickening and facial form in Paranthropus: Examination of alternative developmental models

Paranthropus is distinctive among hominoids in its possession of a greatly thickened hard palate. Although traditionally considered a structural adaptation to counter high-magnitude masticatory stress, alternative developmental models are equally viable. Three models of palatal thickening were evaluated in this study. A mechanical model interprets palatal thickening as a compensatory response to increased instability of the midpalatal suture effected by an anterior placement of the masseteric muscle mass. This model predicts that palatal thickness is correlated with the length of the palate posterior to the masseteric tubercle. Two non-mechanical models consider the thickness of the hard palate to be structurally related to and therefore correlated with either 1) the degree to which the premaxilla overlaps the hard palate in the subnasal region or 2) the height of the posterior facial skeleton. The correlation of craniofacial variables was assessed intraspecifically in ontogenetic series of great ape and human crania. Tests of correlation were performed for each comparison using both residuals calculated from reduced major axis regression of the variable of interest against a measure of cranial size and shape ratios. A significant correlation of palatal thickness with posterior facial height in Pan suggests that the unusually thick hard palate of Paranthropus is directly related to the increased posterior facial height characteristic of this taxon. Further evaluation suggests that extreme palatal thickening in these specimens occurred by virtue of their possession of a nasal septum morphology in which the vomer extends onto the superior nasal surface of the premaxilla. Such a morphology would have constrained the palatal nasal lamina to maintain the approximate level of the premaxillary nasal lamina throughout the growth process thereby promoting palatal thickening. Am J Phys Anthropol 103:375–392, 1997. © 1997 Wiley-Liss, Inc.     

A morphometric analysis of craniofacial growth and changes in spatial relations during secondary palatal development in human embryos and fetuses

Staged human embryos and fetuses in the Carnegie Embryological Collection were morphometrically analyzed to show craniofacial dimensions and changes in spatial relations, and to identify patterns that would reflect normal developmental events during palatal formation. Normal embryos aged 7-8 weeks postconception (Streeter-O'Rahilly stages 19-23) and fetuses aged 9-10 weeks postconception, in eight groups with mean crown-rump (CR) lengths of 18-49 mm, were studied with cephalometric methods developed for histologic sections. In the 4-week period studied, facial dimensions increased predominantly in the sagittal plane with extensive changes in length (depth) and height, but limited changes in width. Growth of the mandible was more rapid than the nasomaxillary complex, and the length of Meckel's cartilage exceeded the length of the oronasal cavity at the time of horizontal movement of the shelves during stage 23. Simultaneously with shelf elevation, the upper craniofacial complex lifted, and the tongue and Meckel's cartilage extended forward beneath the primary palate. Analysis of spatial relations in the oronasal cavity showed that the palatomaxillary processes became separated from the tongue--mandibular complex as the head extended, and the tongue became positioned forward with growth of Meckel's cartilage. As the head position extended by 35 degrees, the cranial base angulation was unchanged and the primary palate maintained a 90 degrees position to the posterior cranial base. However, the sagittal position of the maxilla relative to the anterior cranial base increased by 20 degrees between stages 19 and 23. In the late embryonic and early fetal periods, the mean cranial base angulation of approximately 128 degrees and the mean maxillary position angulation of approximately 84 degrees were similar to the angulations previously shown to be present later prenatally and post-natally. The results suggest that human patterns of cranial base angulation and maxillary position to the cranial base develop during the late embryonic period when the chondrocranium and Meckel's cartilage form the primary skeleton.