Growth and Development at the Sphenoethmoidal Junction in Perinatal Primates.

Integration of the sphenoid and ethmoid bones during early postnatal development is poorly described in the literature. A uniquely prolonged patency of sphenoethmoidal synchondrosis or prespheno-septal synchondrosis (PSept) has been attributed to humans. However, the sphenoethmoidal junction has not been studied using a comparative primate sample. Here, we examined development of the sphenoethmoidal interface using ontogenetic samples of Old and New World monkeys, strepsirrhine primates (lemurs and lorises), and a comparative sample of other mammals. Specimens ranging from late fetal to 1 month postnatal age were studied using histology, immunohistochemistry, and micro-computed tomography methods. Our results demonstrate that humans are not unique in anterior cranial base growth at PSept, as it is patent in all newborn primates. We found two distinctions within our sample. First, nearly all primates exhibit an earlier breakdown of the nasal capsule cartilage that abuts the orbitosphenoid when compared to nonprimates. This may facilitate earlier postnatal integration of the basicranium and midface and may enhance morphological plasticity in the region. Second, the PSept exhibits a basic dichotomy between strepsirrhines and monkeys. In strepsirrhines, the PSept has proliferating chondrocytes that are primarily oriented in a longitudinal plane, as in other mammals. In contrast, monkeys have a convex anterior end of the presphenoid with a radial boundary of cartilaginous growth at PSept. Our findings suggest that the PSept acts as a "pacemaker" of longitudinal facial growth in mammals with relatively long snouts, but may also contribute to facial height and produce a relatively taller midface in anthropoid primates. Anat Rec, 300:2115-2137, 2017. © 2017 Wiley Periodicals, Inc.

Growth factor signaling alters the morphology of the zebrafish ethmoid plate.

Craniofacial development relies on coordinated tissue interactions that allow for patterning and growth of the face. We know a priori that the Wingless, fibroblast growth factor, Hedgehog and transforming growth factor-beta growth factor signaling pathways are required for the development of the face, but how they contribute to the shape of the face is largely untested. Here, we test how each signaling pathway contributes to the overall morphology of the zebrafish anterior neurocranium. We tested the contribution of each signaling pathway to the development of the ethmoid plate during three distinct time periods: the time of neural crest migration [10 hour post fertilization (hpf)]; once the neural crest is resident in the face (20 hpf); and finally at the time at which the cartilaginous condensations are being initiated (48 hpf). Using geometric morphometric analysis, we conclude that each signaling pathway contributes to the shape, size and morphology of the ethmoid plate in a dose-, and time-dependent fashion.

Visualization of craniofacial development in the sox10: kaede transgenic zebrafish line using time-lapse confocal microscopy.

Vertebrate palatogenesis is a highly choreographed and complex developmental process, which involves migration of cranial neural crest (CNC) cells, convergence and extension of facial prominences, and maturation of the craniofacial skeleton. To study the contribution of the cranial neural crest to specific regions of the zebrafish palate a sox10: kaede transgenic zebrafish line was generated. Sox10 provides lineage restriction of the kaede reporter protein to the neural crest, thereby making the cell labeling a more precise process than traditional dye or reporter mRNA injection. Kaede is a photo-convertible protein that turns from green to red after photo activation and makes it possible to follow cells precisely. The sox10: kaede transgenic line was used to perform lineage analysis to delineate CNC cell populations that give rise to maxillary versus mandibular elements and illustrate homology of facial prominences to amniotes. This protocol describes the steps to generate a live time-lapse video of a sox10: kaede zebrafish embryo. Development of the ethmoid plate will serve as a practical example. This protocol can be applied to making a time-lapse confocal recording of any kaede or similar photoconvertible reporter protein in transgenic zebrafish. Furthermore, it can be used to capture not only normal, but also abnormal development of craniofacial structures in the zebrafish mutants.

Distinct requirements for wnt9a and irf6 in extension and integration mechanisms during zebrafish palate morphogenesis.

Development of the palate in vertebrates involves cranial neural crest migration, convergence of facial prominences and extension of the cartilaginous framework. Dysregulation of palatogenesis results in orofacial clefts, which represent the most common structural birth defects. Detailed analysis of zebrafish palatogenesis revealed distinct mechanisms of palatal morphogenesis: extension, proliferation and integration. We show that wnt9a is required for palatal extension, wherein the chondrocytes form a proliferative front, undergo morphological change and intercalate to form the ethmoid plate. Meanwhile, irf6 is required specifically for integration of facial prominences along a V-shaped seam. This work presents a mechanistic analysis of palate morphogenesis in a clinically relevant context.

Embryonic development of the skull of the Andean lizard Ptychoglossus bicolor (Squamata, Gymnophthalmidae).

The study of cranial design and development in Gymnophthalmidae is important to understand the ontogenetic processes behind the morphological diversity of the group and to examine the possible effects of microhabitat use and other ecological parameters, as well as phylogenetic constraints, on skull anatomy. Complete morphological descriptions of embryonic skull development within Gymnophthalmidae are non-existent. Likewise, very little is known about the complete chondrocranium of the family. Herein, the development of the skull of the semi-fossorial lizard Ptychoglossus bicolor is described along with an examination of the chondrocranium of other gymnophthalmid taxa and the teiid Cnemidophorus lemniscatus. Cranial chondrification begins with early condensations in the ethmoid, orbitotemporal and occipital regions of the chondrocranium as well as the viscerocranium. Ossification of the skull starts with elements of the dermatocranium (pterygoid, prefrontal, maxilla and jugal). The orbitosphenoid is the last chondral bone to appear. At birth, the skull is almost completely ossified and exhibits a large frontoparietal fontanelle. In general terms, the chondrocranium of the gymnophthalmids studied is characteristic of lacertiform terrestrial lizards, in spite of their life habits, and resembles the chondrocranium of C. lemniscatus in many aspects. However, the gymnophthalmids show great variation in the orbitosphenoid and a complex nasal capsule. The latter exhibits greater development of some nasal cartilages, which make it more complex than in C. lemniscatus. These characteristics might be related to microhabitat use and the well-developed olfactory and vomeronasal systems observed within this clade.

Revisiting human nose anatomy: phylogenic and ontogenic perspectives.

This review suggests revisiting nose anatomy by considering the ethmoidal labyrinths as part of the olfactory nose and not as paranasal sinuses. Phylogenetically, the olfactory and respiratory organs of the most primitive vertebrates are separated. Exaptation, a mechanism of evolution, may explain the fusion of the olfactory and respiratory organs in dipnoi. The respiratory and olfactory noses remain anatomically separated by the transverse lamina in most mammals, whose olfactory labyrinth is a blind recess housing the ethmoturbinates. In humans, the partitioning between the olfactory cleft and the ethmoid labyrinth seems to be a consequence of ethmoid bone remodeling induced by the acquisition of an upright posture. The ethmoid bone is derived from the cartilaginous nasal capsule of primitive vertebrates and considered to be a highly conserved region among the bony elements of the skull base. It appears to be involved only in housing and protecting the olfactory function. During the early stages of human fetal development, rupture of the oronasal membrane leads to the integration of the primary olfactory sac in the future respiratory organ. The cartilaginous nasal capsule appears in the tissue under the brain and around the olfactory channels. Its early fetal development is classically regarded as the beginning of paranasal sinus formation. From phylogenic and ontogenic perspectives, it may be regarded as the development of the olfactory labyrinth as modified by the remodeling process of the human face and skull base. The endochondral bony origin of the ethmoid labyrinths makes them substantially different from the other paranasal sinuses.

Expression of olfactory receptors in the cribriform mesenchyme during prenatal development.

Olfactory receptors (ORs) are expressed in sensory neurons of the nasal epithelium, where they are supposed to be involved in the recognition of suitable odorous compounds and in the guidance of outgrowing axons towards the appropriate glomeruli in the olfactory bulb. During development, some olfactory receptor subtypes have also been found in non-sensory tissues, including the cribriform mesenchyme between the prospective olfactory epithelium and the developing telencephalon, but it is elusive if this is a typical phenomenon for ORs. Monitoring the onset and time course of expression for several receptor subtypes revealed that 'extraepithelial' expression of ORs occurs very early and transiently, in particular between embryonic stages E10.25 and E14.0. In later stages, a progressive loss of receptor expressing cells was observed. Molecular phenotyping demonstrated that the receptor expressing cells in the cribriform mesenchyme co-express key elements, including Galpha(olf), ACIII and OMP, characteristic for olfactory neurons in the nasal epithelium. Studies on transgenic OMP/GFP-mice showed that 'extraepithelial' OMP/GFP-positive cells are located in close vicinity to axon bundles projecting from the nasal epithelium to the presumptive olfactory bulb. Moreover, these cells are primarily located where axons fasciculate and change direction towards the anterior part of the forebrain.

Cranial base growth and morphology in second-trimester normal human fetuses and fetuses with cleft lip.

OBJECTIVE: The present radiographic study describes the size and shape of the cranial base from the sagittal aspect for a sample of 77 second-trimester "normal" control fetuses (n = 61) and fetuses (n = 16) exhibiting isolated, unilateral clefts of the lip (CL), ranging in fertilization age from 10 to 22 weeks. METHODS: Fetuses were placed in a cephalostat, and standardized, lateral head radiographs were taken. The radiographs were traced, and 15 cephalometric landmarks were identified and digitized for analysis. Growth curves for cranial base lengths, angles, and areas were compared between control and CL groups. Also, cranial base triangles were constructed and shape comparisons were made using tensor biometric analysis. RESULTS: No significant differences (p >.05) in regression line slopes were noted for any comparisons between the control and CL samples. Tensor biometric analysis also revealed no significant differences in the shapes of various cranial base triangles between the control and CL samples. CONCLUSION: This report presents second-trimester baseline growth curves for various cranial base components in CL human fetal specimens, and these data suggest that CL fetuses may also be used as an appropriate control sample for prenatal growth comparison studies of cleft lip and palate and cleft palate.

The spectrum of minimal clefting: process-oriented cleft management in the presence of an intact alveolus.

The minimal cleft lip provides a model for study of the clefting process. Nasolabial embryogenesis can be best understood using the concept of embryonic fields in which midline structures (columella, philtrum, premaxilla, septum, vomer, and ethmoids) develop with paired, fused A fields. Anatomic features of the minimal cleft lip suggest that the actual clefting site is located at the interface between the A and B fields within the lateral piriform wall. Study of the progression of clefting, using this model, places the timing of the clefting event to Carnegie stage 14. The degree to which this initial event affects subsequent fusion of the lateral and medial nasal processes (D and C fields) determines the final morphology of the cleft. Using this model, a rational basis is presented for the surgical management of minimal clefting in its varying manifestations.

Spatial and temporal distribution of cellular proliferation in the cranial base of normal and midfacially retrusive mice.

The craniofacial region of the Brachyrrhine (Br) mouse is characterized by a retruded midface. The cellular mechanism causing this growth deficiency is unknown. However, the cranial base is foreshortened in adult Br mice. The purpose of this study was to determine whether the spatial and temporal patterns of cellular proliferation in the cranial base (CB) differ between normal (C3H/HeJ) and Br mutant (3H1 Br/+) embryonic mice. Twenty-four dams were injected (3)H thymidine (5 microCi/gram body weight) and 15 embryos from each group were collected at Theiler stages 23, 25, and 27 (15, 17, and 19 days of gestation). Serial sections from each head were processed with routine autoradiography. Labelling indices (LI) were determined for each specimen and cellular proliferation maps were generated for each age group. LI patterns within and between groups were compared statistically. Results showed that cellular proliferation in the CB of normal embryos displayed a time- and position-dependent pattern, characteristic of transient growth sites (TGS). Generally, as age increases, cellular proliferative activities decrease gradually (from an average LI of 11.4 +/- 5.7% at stage 23 to 4.4 +/- 2.2% at stage 27), and the number of the TGS decreases in the presumptive nasal septal region and increases in presumptive sphenoethmoidal area with age, indicating the existence of cellular subpopulations in the CB. Cellular proliferation in the CB of the Br mutant displays a different growth pattern compared to the normal condition. Deficiencies in cellular proliferation exist mainly in the presumptive sphenoethmoidal area of the CB. The results indicate that the TGS play an important role in the normal morphogenesis of the CB, and abnormalities in their timing and/or position may be responsible for the dysmorphology of the midface in the Br mutant.

Development of the cribriform plate and of the lamina mediana.

The development of the cribriform plate and lamina mediana was studied in macerated isolated ethmoid bones in specimens from late fetal life to the stage of its final shape (60 specimens). From fetal life to the first year of age, the ethmoid bone consisted of two separate symmetrical halves which had joined together by the end of the first year. Each half of the future ethmoid bone incorporated the superior, middle and occasionally also the supreme nasal concha. The ossification of the cribriform plate started in the new-born where it initially displayed a vertical position but became horizontal in the course of the first year. At the end of the first year both halves of the ethmoid bone had been united by the formation of the crista galli, lamina mediana and complete ossification of the cribriform plate. The lamina mediana reached its final shape by ten years of age. Each half of the ethmoid bone displayed furrows for the fila olfactoria in the region of the superior and occasionally also of the anterior part of the middle nasal concha. The furrows run in a postero-anterior direction. In the course of our investigations we found three cases where all three nasal conchae formed a unique block thus proving the common origin of these structures from the cartilaginous nasal capsule.

Ossicula Bertini in human adults.

Remnants of ossicula Bertini in their embryological position, i.e., joined to the ethmoid, were found in three out of 20 adult individuals aged 17-23 years. The ossicles closed the inferior and/or a part of the anterior wall of the sphenoidal sinus, being joined to the wall of the sinus by sutures. The existence of these formations might be of importance in inflammation of the sphenoid sinus, or disease in or around the nasopharynx.

Midline maxillofacial skeleton in human anencephalic fetuses.

The purpose of this study was to describe the midline maxillofacial skeleton (the axial skeleton anterior to the sella turcica) in 15 human anencephalic fetuses (14-19 weeks of gestation) by radiography and histology, and to relate the findings to skeletal patterns in the remaining part of the axial skeleton. Four patterns in the maxillofacial skeleton were recognized: normal structures, slightly deformed (6 cases); cleft palate (3 cases); incomplete nasal septum (3 cases); multilocular ethmoid cartilage (3 cases). No association was found between skeletal patterns in the different parts of the axial skeleton. The study demonstrates the existence of a developmental borderline in the anencephalic axial skeleton in the region of the sella turcica. It is presumed that this borderline indicates the boundary between skeletal tissue developed around the notochord (posterior axial skeleton) and the anterior skeletal components derived from neural crest cells.

Meningioma and sagittal craniosynostosis in an infant: case report.

The occurrence of a frontal base meningioma in a 3-month-old infant seen for the treatment of sagittal craniosynostosis is reported. The association of the two lesions is of interest both because it is unique and may lend support to theories of the cause of some forms of craniosynostosis.

[Organization of the osseous framework of the nasal septum and its homologues. IV-A. The vomero-transversalis and axial palatine systems (during fetal life of various ++pair-hoofed animals)]. / Organizacja zrebu kostnego przegrody nosa oraz jej homologów. IV-A. Systema vomero-transversale et systema palatinum axiale (w zyciu plodowym niektórych ssaków parzystokopytnych).

The aim of this investigation was the differentiation and systematization of the vomer elements in ontogenesis and the comparison with axial palatal system in fishes and reptiles. The collection of pig heads (18 fetal, 10 young, 4 adults) and of cow heads (15 fetal, 6 young, 3 adults) was examined. The methodology was described elsewhere. It has been proved that vomer in ++pair-hoofed mammals as well as parasphenoid in fishes and amphibia, is not a single and uniform element of the skull ++ out a biochemically integrated system (systema vomero-transversale). It has been also proved that in examined ++ mammals as well as in fishes there exists a palato-axiale system. All these monominals elements in mammals, amphibia and +fishes are homologues.

Ossification of the human fetal basicranium.

Previous investigations of prenatal development of the human cranium have not identified the sequence of its ossification. The purpose of the present study was to elucidate the pattern of skeletal maturity of the cranial bones in the midsagittal region anterior to the foramen magnum. This study is based upon a radiographic and histochemical investigation of midsagittal tissue blocks of the cranial bases of 73 human fetuses derived from the first half of the prenatal period. A marked regularity in the ossification pattern of the bones in the midsagittal part of the human cranium was observed. Ossification starts in the frontal bone. The sequence in which the next bones ossify is occipital bone, basisphenoid bone, presphenoid bone, and ethmoid bone. The material was divided into 7 maturity stages devised for this analysis. The stages were related to general fetal size (crown-rump length) and to general fetal maturation (composite number of ossified bones in hand and foot). Skeletal development of the median part of the human cranium is not strictly correlated with the size or the stage of general maturation of the fetuses. Knowledge of normal skeletal development is necessary for understanding anomalies of development.

[Morphology and development of the cranium of Felis silvestris f. catus Linné 1758--a contribution to comparative anatomy of Carnivora. I. Introduction, material and methods, complete cranium and regio ethmoidalis]. / Zur Morphologie und Entwicklung des Craniums von Felis silvestris f. catus Linné 1758--ein Beitrag zur vergleichenden Anatomie der Carnivora. Teil I: Einleitung, Material und Methoden, Gesamtes Cranium and Regio ethmoidalis.

In the present study, the morphology and development of the cartilaginous and osseous cranium of Felis silvestris f. catus is analysed by investigating 2 advanced embryonic stages of 51.1 mm (Felis 1) and 95.5 mm (Felis 2) crown-rump-length, respectively. The heads of Felis 1 and 2 were serially sectioned transversely to produce some models of the cranium and the nasal capsule (wax-plate reconstruction after Born). The investigation of the advanced embryonic cat stages pursues Terry's studies on younger ones of 10 mm to 23.1 mm c.r.l. So, by now, there is an almost complete embryonic series for comparative examination. On the other hand, our knowledge about craniogenesis of fissiped carnivores as a whole will be augmented. The present 1st part of this study gives a detailed description and discussion of the development of the general form of the cranium, the flexures of the skull base, and the ethmoidal region. It is evident that besides general eutherian features, specific characteristics of terrestrial carnivores and felids, resp., can be demonstrated during the development of the embryonic chondrocranium. Special interest lies upon morphogenesis of the whole nasal capsule, which is comparatively short in late embryogenesis, and solum nasi, with its highly differentiated Cartilago ductus nasopalatini and allied structures.

The natural history and pathogenesis of the cranial coronal ring articulations: implications in understanding the pathogenesis of the Crouzon craniostenotic defects.

The craniostenotic birth defects seen in patients with Crouzon syndrome have prompted this developmental study on the system of articulations between the human frontal, sphenoid, and ethmoid bones. The Crouzon facies, including midfacial hypoplasia and exorbitism, have been linked to the premature synostosis of calvarial sutures. However, considerable evidence shows that midfacial positioning is linked to increasing length of the midline cranial base. Thirty-seven typical-for-age (8 to 29 weeks) embryos were histologically prepared, read serially, and three-dimensionally reconstructed to map the so-called coronal ring articulations that continuously join the frontal, sphenoid, and ethmoid bones. A morphologic staging plan was used to show the progressive development of bones and intervening joints. Data show that a coronal ring exists beginning at 8 weeks. Those portions of the ring separating the frontal and sphenoid bones (within the orbit and laterally along the coronal suture) show the typical structure of a five-layered suture. This sutural component of the ring is C-shaped with a cartilaginous bridge between the optic foramina completing the ring. This is the sphenoethmoidal (S-E) synchondrosis of the midline cranial base. It is suggested that this deeply located cartilage joint is the primary site of pathogenesis in the craniostenotic facies and not the coronal sutures which are operated upon. Even though the S-E cartilage would be difficult and potentially morbid to approach surgically, this study would suggest that preoperative computed tomography (CT) of the skull base with special emphasis on the S-E region may provide a better prognosis regarding midface growth effects after surgery. It appears to be the fused S-E synchondrosis and not necessarily the premature closure of the coronal sutures that may tether the midface posteriorly.