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.     

Human prenatal palatal closure related to skeletal maturity of the jaws

The purpose of the present study was to elucidate the stages of skeletal maturation of the maxilla and the mandible at the time of soft tissue palatal closure. Similar studies were not found in the literature. This investigation was based on maxillae and mandibles from 19 human embryos/fetuses selected by visual inspection of palatal structures, eight fetuses "just before palatal closure," and 11 fetuses "just after palatal closure." The findings are related to formerly described skeletal developmental stages in the maxilla, to stages in the symphysis menti region, and to development in the mandibular condylar region. The present study revealed that elevation of the palatal shelves takes place at a specific stage of maxillary skeletal maturity (stage Max III), at a time of mandibular development characterized by absence of condylar cartilage and by constancy in symphysis menti maturity (stage SM I). Knowledge of the normal sequence of prenatal skeletal development is considered essential for understanding the abnormal sequence of skeletal development.     

Morphological observations in normal primary palate and cleft lip embryos in the Kyoto collection

Normal developmental events during human primary palate formation and alterations associated with cleft lip remain poorly defined. The purpose of this study was to analyze serially sectioned human embryos to identify morphological changes during normal palatal closure and alterations associated with failure of palatal formation. Normal and cleft embryos from the histological collection at the Congenital Anomaly Research Center at the University of Kyoto were studied and photographed for detailed evaluation. Seven serially sectioned cleft lip embryos of stages shortly after primary palate formation (Streeter-O'Rahilly stages 19, 20, and 22) with unilateral or bilateral clefts with varying degrees of clefting were studied. In the normal Kyoto embryos, initial nasal fin (epithelial seam) formation was observed between the medial nasal process and the lateral nasal and maxillary processes at stage 17. During stages 18 and 19, the nasal fin epithelium was replaced by an enlarging mesenchymal bridge, as the maxillary processes united with the medial nasal processes to form the primary palate. The most prominent features observed in the cleft embryos were a reduced thickness of mesenchymal bridging between the medial nasal and maxillary processes, with an excessive amount of epithelium at the junctions between these processes. With ingrowth of the maxillary processes, greater cell dispersion and apparent extracellular matrix accumulation were observed in the medial nasal region. During closure of the primary palate, terminal branches of the maxillary nerve crossed the mesenchymal bridge to the medial nasal region. The partial clefts had reduced maxillary ingrowth and smaller union areas with the medial nasal process. Detailed studies of experimental animal models are required to identify regional growth required for contact between the facial prominences, to clarify the mechanisms of mesenchymal ingrowth and epithelial displacement during palatal formation, and to identify local and/or general factors causing alterations that lead to primary palatal clefting.     

Definitive surgical correction of vertical maxillary deficiency

Inferior repositioning of the maxilla to correct vertical maxillary deficiency has been associated with variable degrees of instability and subsequent relapse. Resorption of bone-graft material has been incriminated as the primary cause of postoperative instability. This paper reports on nine patients who have undergone inferior maxillary repositioning resulting in no residual bone contact between the down-fractured maxilla and superior midface. Mean inferior maxillary repositioning was 6.2 mm. Osteotomy gaps were implanted with porous block hydroxyapatite (Interpore 200), and maxillae were rigidly fixed in position with miniplates. No postoperative intermaxillary fixation was utilized in any patient. Follow-up ranged from 11 to 28 months, with a mean of 19.6 months. Cephalometric analyses at follow-up revealed excellent stability of the repositioned maxillae, with a mean vertical relapse of 4.3 percent. No complications were associated with this procedure. The biomechanical rationale contributing to the success of this operative technique is discussed.     

Experimental induction of palate shelf elevation in glutamate decarboxylase 67-deficient mice with cleft palate due to vertically oriented palatal shelf

BACKGROUND: Gamma-aminobutyric acid is an inhibitory neurotransmitter, synthesized by two isoforms of glutamate decarboxylase (GAD), GAD65 and -67. Unexpectedly, inactivation of GAD67 induces cleft palate in mice. Reduction of spontaneous tongue movement resulting from decreased motor nerve activity has been related to the development of cleft palate in GAD67(-/-) fetuses. In the present study, development of cleft palate was examined histologically and manipulated with culture of the maxilla and partial resection of fetal tongue. METHODS: GAD67(-/-) mice and their littermates were used. Histological examination and immunohistochemistry were performed conventionally. Organ culture of the maxilla was carried out as reported previously. Fetuses were maintained alive under anesthesia and tips of their tongues were resected. RESULTS: Elevation of palatal shelves, the second step of palate formation, was not observed in GAD67(-/-) mice. In wild-type mice, GAD67 and gamma-aminobutyric acid were not expressed in the palatal shelves, except in the medial edge epithelium. During 2 days of culture of maxillae dissected from E13.5-E14.0 GAD67(-/-) fetuses, elevation and fusion of the palatal shelves were induced. When E13.5-15.5 mutant fetuses underwent partial tongue resection, the palatal shelves became elevated within 30 min. CONCLUSIONS: These results suggest that the potential for palate formation is maintained in the palatal shelves of GAD67(-/-) fetuses, but it is obstructed by other, probably neural, factors, resulting in cleft palate.     

Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol

Previous studies in rodents have indicated that the facial changes of fetal alcohol syndrome (FAS) closely resemble those of a mild form of holoprosencephaly. In order to examine this relationship in non-human primates, we evaluated a 133-day gestation macaque (Macaca nemestrina) with holoprosencephaly, median cleft lip and palate, and encephalocele. The mother had been given ethanol once per week (1.8 g/kg body weight) from weeks 2 to 19 postconception. Diagnosis of holoprosencephaly was made following ultrasound evaluation for polyhydramnios and delivery of the female fetus by caesarean section. Another fetus of identical age was delivered by caesarean section for use as a control. Both fetuses were studied by anthropometric, gross, radiographic, and histologic techniques. In the fetus exposed to alcohol, no extracranial anomalies were identified and the karyotype was normal. The brain was micrencephalic, with absent olfactory bulbs, tracts, optic nerves and chiasma, fused frontal lobes, and a single, dilated lateral ventricle; a parietooccipital encephalocele consisted of thin, dysplastic cortex bordering the ventricle; the cerebellum was dysplastic and superiorly displaced. Within the craniofacial complex, anophthalmia was bilateral; premaxillary components were absent, palatal shelves separate, the maxillae closeset, and the ethmoid bone small and deformed. Most of these defects are similar to those encountered in humans with holoprosencephaly and support the hypothesis of shared etiologic and pathogenetic relations between the facial anomalies of fetal alcohol syndrome and holoprosencephaly.     

Skull growth and the presence of auxiliary fontanels in rhinolophoid bats (Microchiroptera)

 Cephalometry was used to detect patterns of cranial growth in fetal bats that have been differentially stained for bone and cartilage. Rhinolophoid bats exhibit elaborate nasal cavities with coincidental distortions of the maxilla. The expansion of these cavities creates paired auxiliary fontanels among the nasal, maxillary, and frontal bones. This distortion of the rostrum is also associated with the loss of the lacrimal bones and the modification of the infraorbital foramen into a shallow canal. The use of the head as an acoustical horn is discussed with reference to the ontogeny of echolocation. Accepted: 12 October 1996     

Palatal growth in baboons (Papio cynocephalus anubis)

In this study the structure and development of the palate as observed in a cross-sectional collection of olive baboons (Papio cynocephalus anubis) skulls are described and analyzed using craniometric techniques. Considered are structural functional relationships among different parts of the palate, and between the palate and other parts of the craniofacial skeleton. Several inferences are drawn and speculated upon. These inferences are as follows: odontogenesis affects premaxillary growth the most during late fetal and early postnatal development; maxillary length is significantly affected by development and eruption of the maxillary dentition, whereas maxillary breadth is less affected by dental development. Growth of the palatine bones and nasopharyngeal airway is correlated with dentomasticatory changes; the developmental and functional significance of these correlations is unclear. Further inferences are that growth rates for each palatal component differ for each sex even though lengths of the components relative to total palatal dimensions show no sexual dimorphism. Also, it is determined that maxillary length remains constant, premaxillary length reduces and palatine length increases relative to total palatal length with growth.     

Facial duplication: case, review, and embryogenesis

The craniofacial anatomy of an infant with facial duplication is described. There were four eyes, two noses, two maxillae, and one mandible. Anterior to the single pituitary the brain was duplicated and there was bilateral arhinencephaly. Portions of the brain were extruded into a large frontal encephalocele. Cases of symmetrical facial duplication reported in the literature range from two complete faces on a single head (diprosopus) to simple nasal duplication. The variety of patterns of duplication suggests that the doubling of facial components arises in several different ways: Forking of the notochord, duplication of the prosencephalon, duplication of the olfactory placodes, and duplication of maxillary and/or mandibular growth centers around the margins of the stomatodeal plate. Among reported cases, the female:male ratio is 2:1.     

Long-term skeletal stability after maxillary advancement with distraction osteogenesis using a rigid external distraction device in cleft maxillary deformities

Rigid external distraction is a highly effective technique for correction of maxillary hypoplasia in patients with orofacial clefts. The clinical results after correction of sagittal maxillary deformities in both the adult and pediatric age groups have been stable. The purpose of this retrospective longitudinal cephalometric study was to review the long-term stability of the repositioned maxilla in cleft patients who underwent maxillary advancement with rigid external distraction. Between April 1, 1995, and April 1, 1999, 17 consecutive patients with cleft maxillary hypoplasia underwent maxillary advancement using rigid external distraction. There were 13 male patients and four female patients, with ages ranging from 5.2 to 23.6 years (mean, 12.6 years). After a modified complete high Le Fort I osteotomy and a latency period of 3 to 5 days, patients underwent maxillary advancement with rigid external distraction until proper facial convexity and dental overjet and overbite were obtained. After active distraction, a 3- to 4-week period of rigid retention was undertaken; this was followed by removable elastic retention for 6 to 8 weeks using, during sleep time, an orthodontic protraction face mask. Cephalometric radiographs were obtained preoperatively, after distraction, at 1 year after distraction, and 2 or more years after distraction. The mean follow-up was 3.3 years (minimum, 2.1 years; maximum, 5.3 years). The following measurements were obtained in each cephalogram: three linear horizontal and two linear vertical maxillary measurements, two angular craniomaxillary measurements, and one craniomandibular measurement. Differences between the preoperative and postoperative cephalometric values were analyzed by paired t tests (p < 0.05). The cephalometric analysis demonstrated postoperatively significant advancement of the maxilla. In addition, the mandibular plane angle opened 1.2 degrees after surgery. After the 1- to 3-year follow-up period, the maxilla was stable in the sagittal plane. Minimal anteroposterior growth was observed in the maxilla compared with that exhibited in the anterior cranial base. However, there was significant vertical maxillary growth over the 3-year observation period. The mandibular plane angle tended to decrease during the follow-up period. The cephalometric data from this study support the clinical impression of maxillary stability after maxillary advancement with rigid external distraction in cleft patients. This effective and stable technique is now considered for all pediatric patients with severe cleft maxillary hypoplasia and for adolescent and adult patients with moderate to severe deformities.     

Reexamination of the immature hominid maxilla from Tangier,Morocco

Reexamination of the immature Upper Pleistocene hominid maxilla from Mugharet el-'Aliya (Tangier), Morocco is undertaken in light of new evidence on the growth and development of Upper Pleistocene hominids. Metric and qualitative comparisons were made with 17 immature Upper Pleistocene maxillae, and with a recent Homo sapiens sapiens sample. No unambiguous criteria for aligning the maxilla with Neandertals were found, although one character, the degree of maxillary flexion on the zygoma, strongly suggests that this child could be a representative of H. s. sapiens. The probable lack of a canine fossa in Mugharet el-'Aliya 1, the primary criterion used previously to align it with Neandertals, cannot be accurately extrapolated to its adult form from this juvenile. The present evidence suggests that it is inappropriate to refer to this fossil as “Neandertal-like” or as a North African “neandertaloid.” Thus, the Tangier maxilla should not be cited as evidence for the presence of Neandertal facial features in North Africa during the Upper Pleistocene. © 1993 Wiley-Liss, Inc.     

Modified technique of presurgical infant maxillary orthopedics for complete bilateral cleft lip and palate

This article introduces technical modifications to the conventional presurgical infant maxillary orthopedics device for newborns with complete bilateral cleft lip and palate, providing procedural simplicity and efficiency as well as therapeutic efficacy. The modifications incorporate a wax block-out on the stone model prior to device fabrication in a manner that the need for periodic acrylic addition and removal is not required, and thus eliminates the risk of natural maxillary growth restriction during infant maxillary orthopedics treatment. The premaxilla is completely excluded from the acrylic palatal plate and is repositioned primarily by the bilateral labial tape alone. In addition, nasal stent wires are installed on the same day of the palatal plate delivery to establish a tripod-like retention mechanism for the intraoral device to be able to replace the conventional mechanical lock-type retention methods. Applying these modifications, infant maxillary orthopedics treatment objectives for bilateral cleft lip and palate can be successfully achieved within 8 weeks of treatment, and the definitive primary cleft lip repair can be performed within 3-4 months of infant maxillary orthopedics treatment at our Center.     

Developmental change in the position of the fetal human larynx

The position of the mammalian larynx has been shown to be an important determinant in breathing, swallowing, and vocalizing patterns. While the growth of the adult human larynx has been studied extensively, detailed examination of fetal development has not been undertaken. Thus, crucial developmental change in the fetal period and the effects of this change on normal maturation are still unclear. This study has examined the development of the larynx and its topography during the fetal period. Thirty specimens were preserved in 10% buffered formaldehyde solution for a period of 6 weeks, after which mid-sagittal sections were performed. Fetal ages were calculated from femur diaphyseal lengths and ranged from 15 to 29 weeks. Direct measurements were taken to determine the growth and position of the larynx and trachea relative to the vertebral column and soft palate. Results show that the upper and lower levels of the larynx correspond to the basiocciput and the lower border of the third to upper border of the fourth cervical vertebrae, respectively. The epiglottic cartilage was present at 15 weeks. By 21 weeks, the epiglottis was well developed and in close palatal apposition. At 23 to 25 weeks, the epiglottis and soft palate were found to be in full contact. The acquisition of this contact may be related to fetal respiratory viability.     

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 nasopalatine ducts and associated structures in the rhesus monkey (Macaca mulatta): topography, prenatal development, function, and phylogeny

Morphological and developmental characteristics of the rhesus monkey nasopalatine duct system and associated primary palatal structures are described along with functional and phylogenetic considerations. Examination of five adult palates and coronal sections of 13 fetal palates together with dissections of a sixth adult specimen and of a 119-day-old fetal palate reveal that the lateral lobes of the tripartate incisive papilla cover clefts leading into the ducts. The ducts pierce the bony palate to enter the nasal fossae in proximity to the incisive suture. The ontogenetic stability of the duct path reflects the retention of ancient duct and primitive choanae relationships and functionally maintains an optimal oral odorant-to-receptor channel. Sixteen timed pregnancy specimens (35-100 days) provided histological material for documenting rostral nasopalatal development. Duct primordia, identified at 35 days, had by 40 days formed the medial duct walls (conjoined septum-papilla from the primary medial palatal component), the lateral duct walls (maxillary processes), and the rostral walls (fused maxillary-intermaxillary components). The caudal walls derive from the fusion of palatal shelves with the papilla (45 days), thus distinguishing primary and secondary fusion modes. Duct epithelial maturation occurs between 70 and 100 days. The absence of a vomeronasal system is attributed to reduction of olfaction in reproductive behavior, while the presence of the coevolved nasopalatine ducts is linked to the persistence of epiglottal-velar valving. The ducts serve as oral food-odor conduits in otherwise functionally separated respiratory and digestive tracts.     

The common developmental origin and phylogenetic aspects of teeth, rugae palatinae, and fornix vestibuli oris in the mouse

Positional and temporal information is of fundamental importance in understanding the morphogenesis of dentition. In order to determine the fate of epithelial cells localized within specific epithelial thickened regions of the forming mouse maxilla, we analyzed serial histological sections in the frontal plane mouse embryos of 12-15 days' gestation. The epithelial thickening of the oral surface of the maxilla from 12-day embryos was spatially delineated and termed the odontogenic epithelial zone (OEZ). Beginning with 12-day embryos, analyses of camera lucida drawings indicated that the OEZ dissociates into anterior (diastema region) and posterior (molariform tooth organ region) epithelial aggregates that form plate-like configurations. The epithelial plates subsequently divide in a mediolateral direction into the epithelial anlagen of rugae palatinae, teeth, and fornix vestibuli oris superior. The medial and lateral parts of the m1 epithelial anlage are situated in dorsal continuation of both the dental and vestibular laminae of the diastema region. The anlage appears to be of dual origin. The fornix vestibuli oris superior develops from two parts: in the rima oris region from the lip-furrow lined with the vestibular lamina, and in the cheek region from the cheek-furrow in place of fusion of the maxillary and mandibular outgrowths. In 15-day embryos with well-formed secondary palates, the rugae occur, numbering nine on each palatal process. The m1 enamel organ cup excavation is positioned between the level of the fifth extending to the seventh rugae. It appears that the division of the maxillary outgrowth oral epithelial covering into rugae as well as into the dentition anlage is closely related. It is suggested that rugae, the vestibulum oris, and the dentition are developmentally and functionally related, and appear to have a common precursor in both ontogenesis and phylogenesis.     

Biomechanical interactions of different mini-plate fixations and maxilla advancements in the Le Fort I Osteotomy: a finite element analysis

This study investigates the biomechanical interaction of different mini-plate fixation types (shapes/sizes and patterns) with segmental advancement levels on the Le Fort I osteotomy using the non-linear finite element (FE) approach. Nine models were generated under a standard 1-piece LeFort I osteotomy for advancement with 3, 6 and 9 mm distances and four mini-plates with three fixation patterns including LL, LI, and II patterns placed on the maxillae models by integrating computed tomography images and computer-aided design system. The axial and oblique occlusal forces were 250 N applied to each premolar/molar and 125 N applied at 30° inclination to the tooth long axis and from palatal to buccal, respectively. The relative micro-movement values between the two maxillary bone segments and maximum mini-plate stress increased obviously with maxilla advancement increment and the increasing trend can be fitted by exponential curve. The corresponding values in II mini-plate fixation presented apparently high values in all simulated cases. The mini-plate stress concentration locations were found at the bending regions to increase high fracture risk. The mini-plate yield strength can be mapped to a critical (limited) advancement for three types of fixations for safe consideration. This study concluded that L-shaped mini-plates with lateral fixation are recommended to provide better stability. The risk for mini-plate fracture and bone relapse increases when maxillary advancement is larger than a critical value of 5 mm in the Le Fort I osteotomy.     

Functional plasticity of the venom delivery system in snakes with a focus on the poststrike prey release behavior

We explored variations in the morphology and function of the envenomation system in the four families of snakes comprising the Colubroidea (Viperidae, Elapidae, Atractaspididae, and Colubridae) using our own prey capture records and those from the literature. We first described the current knowledge of the morphology and function of venom delivery systems and then explored the functional plasticity found in those systems, focusing on how the propensity of snakes to release prey after the strike is influenced by various ecological parameters. Front-fanged families (Viperidae, Elapidae, and Atractaspididae) differ in the morphology and topographical relationships of the maxilla as well as in the lengths of their dorsal constrictor muscles (retractor vomeris; protractor, retractor, and levator pterygoidei; protractor quadrati), which move the bones comprising the upper jaw, giving some viperids relatively greater maxillary mobility compared to that of other colubroids. Rear-fanged colubrids vary in maxillary rotation capabilities, but most have a relatively unmodified palatal morphology compared to non-venomous colubrids. Viperids launch rapid strikes at prey, whereas elapids and colubrids use a variety of behaviors to grab prey. Viperids and elapids envenomate prey by opening their mouth and rotating both maxillae to erect their fangs. Both fangs are embedded in the prey by a bite that often results in some retraction of the maxilla. In contrast, Atractaspis (Atractaspididae) envenomates prey by extruding a fang unilaterally from its closed mouth and stabbing it into the prey by a downward-backwards jerk of its head. Rear-fanged colubrids envenomate prey by repeated unilateral or bilateral raking motions of one or both maxillae, some aspects of which are kinematically similar to the envenomation behavior in Atractaspis. The envenomation behavior, including the strike and prey release behaviors, varies within families as a function of prey size and habitat preference. Rear-fanged colubrids, arboreal viperids, and elapids tend to hold on to their prey after striking it, whereas atractaspidids and many terrestrial viperids release their prey after striking it. Larger prey are more frequently released than smaller prey by terrestrial front-fanged species. Venom delivery systems demonstrate a range of kinematic patterns that are correlated to sometimes only minor modifications of a common morphology of the jaw apparatus. The kinematics of the jaw apparatus are correlated with phylogeny, but also show functional plasticity relating to habitat and prey.     

Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development

Mammalian palatogenesis is a highly regulated morphogenetic process during which the embryonic primary and secondary palatal shelves develop as outgrowths from the medial nasal and maxillary prominences, respectively, remodel and fuse to form the intact roof of the oral cavity. The complexity of control of palatogenesis is reflected by the common occurrence of cleft palate in humans. Although the embryology of the palate has long been studied, the past decade has brought substantial new knowledge of the genetic control of secondary palate development. Here, we review major advances in the understanding of the morphogenetic and molecular mechanisms controlling palatal shelf growth, elevation, adhesion and fusion, and palatal bone formation.