FGF and EDA pathways control initiation and branching of distinct subsets of developing nasal glands.

Hypertrophy, hyperplasia and altered mucus secretion from the respiratory submucosal glands (SMG) are characteristics of airway diseases such as cystic fibrosis, asthma and chronic bronchitis. More commonly, hyper-secretion of the nasal SMGs contributes to allergic rhinitis and upper airway infection. Considering the role of these glands in disease states, there is a significant dearth in understanding the molecular signals that regulate SMG development and patterning. Due to the imperative role of FGF signalling during the development of other branched structures, we investigated the role of Fgf10 during initiation and branching morphogenesis of murine nasal SMGs. Fgf10 is expressed in the mesenchyme around developing SMGs while expression of its receptor Fgfr2 is seen within glandular epithelial cells. In the Fgf10 null embryo, Steno's gland and the maxillary sinus gland were completely absent while other neighbouring nasal glands showed normal duct elongation but defective branching. Interestingly, the medial nasal glands were present in Fgf10 homozygotes but missing in Fgfr2b mutants, with expression of Fgf7 specifically expressed around these developing glands, indicating that Fgf7 might compensate for loss of Fgf10 in this group of glands. Intriguingly the lateral nasal glands were only mildly affected by loss of FGF signalling, while these glands were missing in Eda mutant mice, where the Steno's and maxillary sinus gland developed as normal. This analysis reveals that regulation of nasal gland development is complex with different subsets of glands being regulated by different signalling pathways. This analysis helps shed light on the nasal gland defects observed in patients with hypohidrotic ectodermal dysplasia (HED) (defect EDA pathway) and LADD syndrome (defect FGFR2b pathway).

Wnt6 is required for maxillary palp formation in Drosophila.

BACKGROUND: Wnt6 is an evolutionarily ancient member of the Wnt family. In Drosophila, Wnt6 loss-of-function animals have not yet been reported, hence information about fly Wnt6 function is lacking. In wing discs, Wnt6 is expressed at the dorsal/ventral boundary in a pattern similar to that of wingless, an important regulator of wing size. To test whether Wnt6 also contributes towards wing size regulation, we generated Wnt6 knockout flies. RESULTS: Wnt6 knockout flies are viable and have no obvious defect in wing size or planar cell polarity. Surprisingly, Wnt6 knockouts lack maxillary palps. Interestingly, Wnt6 is absent from the genome of hemipterans, correlating with the absence of maxillary palps in these insects. CONCLUSIONS: Wnt6 is important for maxillary palp development in Drosophila, and phylogenetic analysis indicates that loss of Wnt6 may also have led to loss of maxillary palps on an evolutionary time scale.

Magnetic resonance imaging evaluation of fetal maxillary sinuses.

BACKGROUND AND OBJECTIVE: The growth of maxillary sinus is closely connected to the development of facial structures. However, its definition and reference standards on fetal magnetic resonance imaging (MRI) have not been analyzed so far. In this study, the objectives were to define and evaluate the fetal maxillary sinus (fMS) formation with MRI. METHODS: We reviewed T2-weighted coronal MRI images of 75 fetuses. The MRI features, time of appearance, and boundaries of fMS were defined. Craniocaudal and transverse diameters of both maxillary sinuses and bone biparietal diameters were measured and statistically evaluated. RESULTS: In 150 fMS site analysis, 91 fMSs were identified. The fMSs were visualized as a hyperintense structures on T2-weighted image above the tooth bud. It first appeared at the 22nd gestational week, and in 4% (3/75) of fetuses, there was unilateral development. Mean craniocaudal length was 2.84 mm (1.1-4.8 mm), and mean transverse diameter was 2.67 mm (1.5-4.2 mm). CONCLUSIONS: Magnetic resonance imaging features of fMS that should be sought for the assessment of craniofacial anatomy are identified in this study. Fetal maxillary sinuses can be observed as hyperintense structures on T2-weighted MRI images starting from 22 weeks of gestation. The growth of fMS follows a predictable course throughout gestation; however, the dimensions are larger than the previously reported ex vivo series.

Partial congenital arrhinia: never seen before adult presentation.

BACKGROUND: Arrhinia is defined as the partial or complete absence of the nasal structures. It is a defect of embryonal origin and can be seen in association with other craniofacial anomalies, central nervous system anomalies, absence of paranasal sinuses, and other palatal and ocular abnormalities. Very few patients with arrhinia have been reported so far in the history of modern medicine. CASE REPORT: This study reports an adult patient with congenital partial arrhinia and reviews the literature along with the embryological basis of such a rare disease. CONCLUSION: Arrhinia is a medical condition with scarce documentation in the literature. This article presents the clinical as well as radiological features of this rare entity.

Understanding the formation of maxillary sinus in Japanese human foetuses using cone beam CT.

The formation of the maxillary sinus (MS) is tied to the maturation of the craniofacial bones during development. The MS and surrounding bone matrices in Japanese foetal specimens were inspected using cone beam computed tomography relative to the nasal cavity (NC) and the surrounding bones, including the palatine bone, maxillary process, inferior nasal concha and lacrimal bone. The human foetuses analysed were 223.2 ± 25.9 mm in crown-rump length (CRL) and ranged in estimated age from 20 to 30 weeks of gestation. The amount of bone in the maxilla surrounding the MS increased gradually between 20 and 30 weeks of gestation. Various calcified structures that formed the bone matrix were found in the cortical bone of the maxilla, and these calcified structures specifically surrounded the deciduous tooth germs. By 30 weeks of gestation, the uncinate process of the ethmoid bone formed a border with the maxilla. The distance from the midline to the maximum lateral surface border of the MS combined with the width from the midline to the maximum lateral surface border of the inferior nasal concha showed a high positive correlation with CRL in Japanese foetuses. There appears to be a complex correlation between the MS and NC formation during development in the Japanese foetus. Examination of the surrounding bone indicated that MS formation influences maturation of the maxilla and the uncinate process of the ethmoid bone during craniofacial bone development.

Maxillary sinus development in patients with cleft palates as compared to those with normal palates.

Maxillary sinusitis appears to be more prevalent in the cleft palate population than in the normal population. The increase in sinusitis may be due to the fact that the maxillary sinus develops differently embryonically in cleft palate patients than in those patients with normal palates. A double blind study was done by measuring the maxillary sinus cephalometric x-rays in cleft palate patients and then comparing them to patients with normally developed palates. The groups studied were 3 months to 20 years of age. It was concluded that in each of these groups there was no significant difference in size, shape, or rate of development of the maxillary sinus in cleft palate patients compared to the normal population. It is probable that the increased incidence of maxillary sinusitis in cleft palate patients is due mainly to the open palate with constant contamination of the nasal mucosa by food pushed into the nares and sinus ostia, resulting in maxillary sinusitis.

Maxillary sinus hypoplasia, embryology, and radiology.

Maxillary sinus hypoplasia has been observed in up to 10% of radiological studies of the face or head. Although this may be a coincidental finding, it has been associated with chronic sinusitis and facial pain. Associated abnormalities of the lateral nasal wall, orbit, and ostiomeatal complex are common. The importance of this condition is, first, in the differential diagnosis of an "opaque" maxillary sinus and, second, as a potential hazard to the orbit of such patients, should they undergo functional endoscopic sinus surgery.

Morphogenesis of the lateral nasal wall from 6 to 36 weeks.

This research describes the development of the lateral nasal wall, the description of which will allow a better comprehension of its anatomic complexity. One hundred embryos and fetuses from the sixth to thirty-sixth weeks of morphologic age were studied. The seventh week shows the first buds of the three turbinates. At the ninth week the precartilaginous nucleus of the inferior turbinate is observed. Likewise, at the tenth week the uncinate process appears, and the invagination of the epithelium begins the formation of the infundibulum and the maxillar sinus. At the fourteenth week the cartilaginous nasal capsule is present. The epithelium is invaginated, starting the formation of the ethmoid cells. During the seventeenth week of development the invagination of the mucus has invaded the maxillar bone, which constitutes the maxillar sinus. At the thirty-sixth week the lateral nasal wall is well developed. In 23 fetuses the supreme turbinate (fourth) was found. Although the length of the lower three turbinates increased progressively and proportionally in intrauterine life without differences between the sexes, the fourth remains invariably at an average length of 5 mm from the fourteenth to the thirty-sixth and was present in 65% of male fetuses.

Investigations on the growth pattern of the maxillary sinus in Japanese human fetuses.

The growth pattern of the maxillary sinus was analyzed using 18 human fetuses of both sexes between 9 and 21 weeks of age postconception. The paraffin embedded specimens were cut in series in the frontal and the transversal plane, respectively. The inner surface of the maxillary sinuses was redrawn and surrounded with a digitizer and then the volumes were calculated. A correlation analysis as well as a simple linear regression analysis between the values of the maxillary sinus, different linear values of the nasal cavity and the crown-rump length (CRL) served to prove possible growth relations. The maxillary sinus' Anlage was already identifiable in the 29.8 mm (CRL) fetus. From this first appearance, the maxillary sinus expands not only in posterior direction but also in anterior direction from 11 weeks onwards. The maxillary sinus volume increased from 0.0008 mm3 at the age of 9 weeks to more than 9 mm3 at the age of 21 weeks. The results of the statistical analysis indicated, that the relationship between the maxillary sinus' Anlage and the nasal cavity were strongly influenced by the body size (CRL). This study suggests, that the growth of the maxillary sinus follows special regularities in the early fetal development.

Immunocytochemical study of the maxilla and maxillary sinus during human fetal development.

We quantitatively examined the distribution of the proliferating cell nuclear antigen (PCNA), which is associated with cell division, and of components of the ECMs (collagen types I and III, tenascin and osteonectin) in the immature zones at three sites: palatine, inferior and vertical surface region of the fetal human maxilla as well as the maxillary sinus (MS) at 12, 16, 20, 24, and 28 weeks gestation. The percentage of PCNA-positive cells was the highest at 16 weeks in the immature zones of maxilla. Tenascin and fibrillar collagens (collagen types I and III) were especially present in the cellular zone linked to the bone and cartilage matrices of the immature zones of the maxillary bone at 20-24 weeks gestation. The osteonectin was detected on the maxillary bone from 24 weeks. These distributions of ECMs revealed the specific and contrasting profiles of development in the human maxillary bone and might reflect the formation of paranasal sinus as MS.

[Developmental studies on the palatine bone in the human skull. With special references to the development of its nasal surface].

For the purpose of these studies 83 cases of fetus skulls and 4 cases of adult skulls were used and the following results were obtained; The palatine bone was found to ossify in a fetus between the middle of the second month and that of the third month. The pyramidal process and conchal crest were first observed in a 9.0 cm fetus. The orbital process, sphenoidal process, sphenopalatine notch and nasal crest were first found in a 16.0 cm fetus. The ethmoidal crest was first found in a 20.0 cm fetus. The posterior nasal spine was first found in a 33.0 cm fetus. The anterior part of the palatal surface of the horizontal plate was found to cover the posterior part of the nasal surface of the palatine process of the maxilla so as to form two layers one above the other. However, the covered surface gradually reduced in size finally to make the transverse palatine suture between the maxilla and the palatine bone in the adult. The transverse length of the horizontal plate was almost equal to its antero-posterior length up until the fifth month fetus, while the former was constantly longer than the latter in the fetus older than the sixth month. The perpendicular plate was constantly longer than the horizontal plate in the fetus older than the fourth month. The metrical comparison between the fetus and the adult revealed that the most well-developing part of the palate bone was the height of the perpendicular plate, which developed 10.9 times longer than that of the fourth month fetus. The rest of the part developed 4.5-5.5 times longer than that of the fourth month fetus.

Prenatal development of the maxillary sinus: a perspective for paranasal sinus surgery.

OBJECTIVE: To review the prenatal development of the maxillary sinus under the perspective of the sinus surgery. STUDY DESIGN: Cross-sectional study. SETTING: Basic embryology laboratory. SUBJECTS AND METHODS: Morphometry and morphology of the maxillary sinus and its ostium were studied under stereomicroscopy in 100 human fetuses from the 9th to the 37th week. Fetuses were obtained from the Fetal Collection of the School of Medicine of the Universidad Autónoma de Nuevo León. Approval was granted by the Ethics Committee. Statistics were applied. RESULTS: The maxillary sinus begins its development at the 10th week. On the 37th week, the anterior-posterior diameter has a mean of 4.36 mm; ossification of the medial wall was absent, and the floor was located below the attachment of the inferior turbinate. Septa and recesses were temporarily observed. Some variations in shape were observed; however, only the oval shape persisted. Maxillary sinus hypoplasia was not found, although asymmetry was present in 30% of cases. The ostium was located at the anterior third of the ethmoid infundibulum; its final dimensions were 1.96 mm in length and 0.44 mm in width. The mean length between the ostium to the lamina papyracea and nasolacrimal duct was 1 mm. One case of double maxillary sinus was observed. Significant difference between the variables, in accordance with the age, was found (P = .02). CONCLUSION: Knowledge of prenatal development of the maxillary sinus improves the perspective of the sinus surgeon and helps the understanding of postnatal anatomy, especially in children.

The maxillary sinus in three genera of new world monkeys: factors that constrain secondary pneumatization.

The air filled cavities of paranasal sinuses are thought by some to appear opportunistically in spatial "gaps" within the craniofacial complex. Anthropoid primates provide excellent natural experiments for testing this model, since not all species possess a full complement of paranasal sinuses. In this study, two genera of monkeys (Saguinus and Cebuella) which form maxillary sinuses (MS) as adults were compared to squirrel monkeys (Saimiri spp.), in which a MS does not form. Using microCT and histomorphometric methods, the spatial position of paranasal spaces was assessed and size of the adjacent dental sacs was measured. In Saguinus, secondary pneumatization is underway perinatally, and the sinus extends alongside deciduous premolars (dp). The MS overlaps all permanent molars in the adult. In Saimiri, the homologous space (maxillary recess) extends no farther posterior than the first deciduous premolar at birth and extends no farther than the last premolar in the adult. Differences in dental size and position may account for this finding. For example, Saimiri has significantly larger relative dp volumes, and enlarged orbits, which encroach on the internasal space to a greater degree when compared to Saguinus. These factors limit space for posterior expansion of the maxillary recess. These findings support the hypothesis that secondary pneumatization is a novel, opportunistic growth mechanism that removes "unneeded" bone. Moreover, paranasal spaces occur in association with semiautonomous skeletal elements that border more than one functional matrix, and the spatial dynamics of these units can act as a constraint on pneumatic expansion of paranasal spaces.