Novel insights into the development of the avian nasal cavity.

In embryonic amniotes, patterning of the oral and nasal cavities requires bilateral fusion between craniofacial prominences, ensuring an intact primary palate and upper jaw. After fusion has taken place, the embryonic nasal cavities open anteriorly through paired external nares positioned directly above the fusion zones and bordered by the medial nasal and lateral nasal prominences. In this study, we show that in the chicken embryo, the external nares initially form as patent openings but only remain so for a short period of time. Soon after the nasal cavities form, the medial nasal and lateral nasal prominences fuse together in stage 29 embryos, entirely closing off the external nares for a substantial portion of embryonic and fetal development. The epithelium between the fused prominences is then retained and eventually develops into a nasal plug that obstructs the nasal vestibule through the majority of the fetal period. At stage 40, the nasal plug begins to break down through a combination of cellular remodeling, apoptosis, as well as non-apoptotic necrosis, leading to completely patent nasal cavities at hatching. These findings place chickens in a category with several species of nonavian reptiles and mammals (including humans) that have been found to develop a transient embryonic nasal plug. Our findings are discussed in the context of previously reported cases of nasal plugs as part of normal embryonic development and provide novel insight into the craniofacial development of a key model organism in developmental biology.

Comparative growth in the olfactory system of the developing chick with considerations for evolutionary studies.

Despite the long-held assumption that olfaction plays a relatively minor role in the behavioral ecology of birds, crown-group avians exhibit marked phylogenetic variation in the size and form of the olfactory apparatus. As part of a larger effort to better understand the role of olfaction and olfactory tissues in the evolution and development of the avian skull, we present the first quantitative analysis of ontogenetic scaling between olfactory features [olfactory bulbs (OBs) and olfactory turbinates] and neighboring structures (cerebrum, total brain, respiratory turbinates) based on the model organism Gallus gallus. The OB develops under the predictions of a concerted evolutionary model with rapid early growth that is quickly overcome by the longer, sustained growth of the larger cerebrum. A similar pattern is found in the nasal cavity where the morphologically simple (non-scrolled) olfactory turbinates appear and mature early, with extended growth characterizing the larger and scrolled respiratory turbinates. Pairwise regressions largely recover allometric relationships among the examined structures, with a notable exception being the isometric trajectory of the OB and olfactory turbinate. Their parallel growth suggests a unique regulatory pathway that is likely driven by the morphogenesis of the olfactory nerve, which serves as a structural bridge between the two features. Still, isometry was not necessarily expected given that the olfactory epithelium covers more than just the turbinate. These data illuminate a number of evolutionary hypotheses that, moving forward, should inform tradeoffs and constraints between the olfactory and neighboring systems in the avian head.

What does the normal fetal face look like? MR imaging of the developing mandible and nasal cavity.

PURPOSE: Analyze fetal facial structures using MR imaging scans in an aim to establish normal biometrical measures of fetal nasal and mandibular structures for multiple gestational weeks, comprise nomograms and compare female and male fetuses. METHODS: A Historic cohort study of 255 fetal facial MR imaging scans was performed at a tertiary medical center during a 4-year period. Clinical data was collected from electronic medical charts. Length of septal height (SH), septal length (SL), Interocular Distance(IOD), maximal nasal length(MNL), mandibular vertebral length(MVL), antero-posterior diameter(APD), inferior facial angle(IFA) and biparietal diameter(BPD) were measured and compared with gender and gestational age (GA). Interrater and intrarater reliability was investigated. RESULTS: Normal measures were established for each gestational age. We found that all parameters but IFA correlated with GA. Males had a longer SL, BPD and MNL while females had a wider IFA. CONCLUSIONS: Novel facial biometric parameters that correlate with GA hold cardinal information for the prenatal evaluation of facial development and thus surface the need for additional research in order to asses these findings as radiologic markers for facial structural pathologies.

Ontogeny of the Orbital Glands and Their Environs in the Pantropical Spotted Dolphin (Stenella attenuata: Delphinidae).

The nasolacrimal duct (NLD) connects the orbital (often associated with the Deep Anterior Orbital gland: DAOG, a.k.a. Harderian gland) and nasal regions in many tetrapods. Adult cetaceans are usually said to lack an NLD, and there is little agreement in the literature concerning the identity of their orbital glands, which may reflect conflicting definitions rather than taxonomic variation. In this study, we examined an embryological series of the pantropical spotted dolphin (Stenella attenuata), and report numerous divergences from other tetrapods. Underdeveloped eyelids and a few ventral orbital glands are present by late Stage (S) 17. By S 19, circumorbital conjunctival glands are present. In S 20, these conjunctival glands have proliferated, eyelids (and scattered palpebral glands) have formed, and a duct similar to the NLD has appeared. Subsequently, both the palpebral glands and the NLD are progressively reduced by S 22, even as the conjunctival glands exhibit regional growth. In most tetrapods examined, the ontogeny of the NLD follows a series of three stages: Inception of NLD, Connection of orbit and nasal cavity by the NLD and Ossification (i.e., formation of the bony canal surrounding the NLD, emerging into the orbit via the lacrimal foramen in the lacrimal bone). In contrast, the dolphin NLD originates at the same time as the lacrimal bone, and a lacrimal foramen fails to develop. The cetacean fossil record shows that a lacrimal foramen was present in the earliest ancestral amphibious, freshwater forms, but was soon lost as the lineage invaded the oceans. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:77-87, 2018. © 2017 Wiley Periodicals, Inc.

Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis.

BACKGROUND: Mutations of WNT3, WNT5A, WNT9B, and WNT11 genes are associated with orofacial birth defects, including nonsyndromic cleft lip with cleft palate in humans. However, the source of Wnt ligands and their signaling effects on the orofacial morphogenetic process remain elusive. RESULTS: Using Foxg1-Cre to impair Wnt secretion through the inactivation of Gpr177/mWls, we investigate the relevant regulation of Wnt production and signaling in nasal-facial development. Ectodermal ablation of Gpr177 leads to severe facial deformities resulting from dramatically reduced cell proliferation and increased cell death due to a combined loss of WNT, FGF and BMP signaling in the developing facial prominence. In the invaginating nasal pit, the Gpr177 disruption also causes a detrimental effect on migration of the olfactory epithelial cells into the mesenchymal region. The blockage of Wnt secretion apparently impairs the olfactory epithelial cells through modulation of JNK signaling. CONCLUSIONS: Our study thus suggests the head ectoderm, including the facial ectoderm and the neuroectoderm, as the source of canonical as well as noncanonical Wnt ligands during early development of the nasal-facial prominence. Both ß-catenin-dependent and -independent signaling pathways are required for proper development of these morphogenetic processes.

Morphology of the nasal capsule of primates--with special reference to Daubentonia and Homo.

Primitive mammals are considered macrosmatic. They have very large and complicated nasal capsules, nasal cavities with extensive olfactory epithelia, and relatively large olfactory bulbs. The complicated structures of the nasal capsule follow a relatively conservative "bauplan," which is normally easy to see in earlier fetal stages; especially in altricial taxa it differentiates well into postnatal life. As anteriormost part of the chondrocranium, the nasal capsule is at first cartilaginous. Most of it ossifies endochondrally, but "appositional bone" ("Zuwachsknochen") is also common. Many fetal structures become resorbed. Together, all surviving bone structures form the ethmoid bone, but cartilages of the external nose and of the vomeronasal complex can persist throughout life. We describe in detail the anatomy of Daubentonia madagascariensis based on a fetal stage (41 mm HL) and an adult skull was analyzed by µCT. We found that the nasal capsule of this species is by far the most complicated one of all extant Primates. We also describe older fetuses of Homo sapiens (35 and 63 mm HL) as representative of a derived primate. The most significant feature of man--and probably of all anthropoids--is the complete loss of the recessus frontoturbinalis and its associated structures. It can be demonstrated that the evolutionary reductions within the primate nasal capsule mainly affect those structures associated with olfaction, whereas cartilages that are important for the biomechanics of the facial skull of the fetus persist.

The nasal cavity of the sheep and its olfactory sensory epithelium.

Macro and microdissection methods, conventional histology and immunohistochemical procedures were used to investigate the nasal cavity and turbinate complex in fetal and adult sheep, with special attention to the ethmoturbinates, the vestibular mucosa, and the septal mucosa posterior to the vomeronasal organ. The ectoturbinates, which are variable in number and size, emerge and develop later than the endoturbinates. The olfactory sensory epithelium is composed of basal cells, neurons, and sustentacular cells organized in strata, but numerous different types are distinguishable on the basis of their thickness and other properties; all variants are present on the more developed turbinates, endoturbinates II and III. Mature neurons and olfactory nerve bundles express olfactory marker protein. We found no structure with the characteristics that in mouse define the septal organ or the ganglion of Grüneberg. Our results thus suggest that in sheep olfactory sensory neurons are exclusively concentrated in the main olfactory epithelium and (to a lesser extent) in the vomeronasal organ.

Morphological characterization of the nasopalatine region in human fetuses and its association to pathologies.

UNLABELLED: The nasopalatine region is composed of structures such as the vomeronasal organ and nasopalatine duct. The nasopalatine duct may provide the communication of the mouth to the nasal cavity in human fetuses and can be obliterated in an adult human. Knowledge on the development of the nasopalatine region and nasopalatine duct in humans is necessary for understanding the morphology and etiopathogenesis of lesions that occur in this region. OBJECTIVE: The aim of the present study was to describe the morphological aspects of the nasopalatine region in human fetuses and correlate these aspects with the development of pathologies in this region. MATERIAL AND METHODS: Five human fetuses with no facial or palatine abnormalities were used for the acquisition of specimens from the nasopalatine region. After demineralization, the specimens were histologically processed. Histological cuts were stained with methylene blue to orient the cutting plane and hematoxylin-eosin for the descriptive histological analysis. RESULTS: The age of the fetuses was 8.00, 8.25, 9.00 and 9.25 weeks, and it was not possible to determine the age in the last one. The incisive canal was observed in all specimens as an opening delimited laterally by the periosteum and connecting oral and nasal cavity. The nasopalatine duct is an epithelial structure with the greatest morphological variation, with either unilateral or bilateral occurrence and total patent, partial patent and islet forms. The vomeronasal organ is a bilateral epithelized structure located alongside the nasal septum above the incisive canal in all the fetuses. CONCLUSIONS: The incisive canal, nasopalatine duct and vomeronasal organ are distinct anatomic structures. The development of nasopalatine duct cysts may occur in all forms of the nasopalatine duct.

Morphological characterization of the nasopalatine region in human fetuses and its association to pathologies

The nasopalatine region is composed of structures such as the vomeronasal organ and nasopalatine duct. The nasopalatine duct may provide the communication of the mouth to the nasal cavity in human fetuses and can be obliterated in an adult human. Knowledge on the development of the nasopalatine region and nasopalatine duct in humans is necessary for understanding the morphology and etiopathogenesis of lesions that occur in this region. Objective The aim of the present study was to describe the morphological aspects of the nasopalatine region in human fetuses and correlate these aspects with the development of pathologies in this region. Material and Methods Five human fetuses with no facial or palatine abnormalities were used for the acquisition of specimens from the nasopalatine region. After demineralization, the specimens were histologically processed. Histological cuts were stained with methylene blue to orient the cutting plane and hematoxylin-eosin for the descriptive histological analysis. Results The age of the fetuses was 8.00, 8.25, 9.00 and 9.25 weeks, and it was not possible to determine the age in the last one. The incisive canal was observed in all specimens as an opening delimited laterally by the periosteum and connecting oral and nasal cavity. The nasopalatine duct is an epithelial structure with the greatest morphological variation, with either unilateral or bilateral occurrence and total patent, partial patent and islet forms. The vomeronasal organ is a bilateral epithelized structure located alongside the nasal septum above the incisive canal in all the fetuses. Conclusions The incisive canal, nasopalatine duct and vomeronasal organ are distinct anatomic structures. The development of nasopalatine duct cysts may occur in all forms of the nasopalatine duct. .

Illustrated review of the embryology and development of the facial region, part 1: Early face and lateral nasal cavities.

The early embryological development of the face has been reviewed. One repeating theme to note is the serial closing and then the re-opening of a space. This is seen in the separation of the nasal and oral cavities, the nostrils, and in part 2 the developing eyelids fusing and then re-opening. Part 2 will discuss the further facial development as well as the changes in facial bone appearance after birth.

Congenital nasal obstruction: clinical and radiologic review.

Congenital nasal obstruction can result in neonatal respiratory distress because neonates are obligate nasal breathers. Therefore, all physicians who deal with infants should be familiar with the structural abnormalities, masses, and syndromes that cause nasal obstruction, so that appropriate work-up and treatment can be promptly initiated. This paper reviews the embryology of the nasal passage and then continues with the different causes of nasal obstruction. Special attention is paid to the presentation, physical exam findings, and imaging modality of choice.

ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis.

p63, a member of p53 family, has a significant role in the development and maintenance of stratified epithelia. However, a persistent dispute remained over the last decade concerning the interpretation of the severe failure of p63-null embryos to develop stratified epithelia. In this study, by investigating both p63-deficient strains, we demonstrated that p63-deficient epithelia failed to develop beyond ectodermal stage as they remained a monolayer of non-proliferating cells expressing K8/K18. Importantly, in the absence of p63, corneal-epithelial commitment (which occurs at embryonic day 12.5 of mouse embryogenesis) was hampered 3 weeks before corneal stem cell renewal (that begins at P14). Taken together, these data illustrate the significant role of p63 in epithelial embryogenesis, before and independently of other functions of p63 in adult stem cells regulation. Transcriptome analysis of laser captured-embryonic tissues confirmed the latter hypothesis, demonstrating that a battery of epidermal genes that were activated in wild-type epidermis remained silent in p63-null tissues. Furthermore, we defined a subset of novel bona fide p63-induced genes orchestrating first epidermal stratification and a subset of p63-repressed mesodermal-specific genes. These data highlight the earliest recognized action of ΔNp63 in the induction epidermal morphogenesis at E11.5. In the absence of p63, a mesodermal program is activated while epidermal morphogenesis does not initiate.

Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and in the nasal cavity of the mouse.

The aim of this study was to analyse the hitherto largely unknown expression patterns of some specific cellular and extracellular molecules during palate and nasal cavity development. We showed that epithelia of the developing palate and the vomerine epithelium express similar sets of structural proteins. With the exception of keratin 15, which becomes barely detectable in the elevated palatal shelves, nearly all of these proteins become upregulated at the presumptive areas of fusion and in the adhering epithelia of the palate and nasal septum. In vivo and in vitro analyses indicated that reduction in the amount of keratin 15 protein is independent of Tgfbeta-Alk5 signalling. Foxa1 expression also highlighted the regionalization of the palatal and nasal epithelia. Owing to the lack of reliable markers of the palatal periderm, the fate of peridermal cells has been controversial. We identified LewisX/stage-specific embryonic antigen-1 as a specific peridermal marker, and showed that numerous peridermal cells remain trapped in the medial epithelial seam (MES). The fate of these cells is probably apoptosis together with the rest of the MES cells, as we provided strong evidence for this event. Heparan sulphate, chondroitin-6-sulphate, and versican displayed dynamically changing distribution patterns. The hitherto-unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting.

Morphometric analyses of the development of nasal cavity in human fetuses: an anatomical and radiological study.

OBJECTIVE: It was aimed to research the morphometric development of the nasal cavity with dissection and radiological scanning methods and to detect anatomical variations. DESIGN: Retrospective study. SETTING: Departments of Anatomy and Radiology, Meram Medical Faculty, Selcuk University. PATIENTS: Dissection stage was performed on 80 spontaneously aborted fetuses (40 males and 40 females) (63 second trimesters and 17 third trimesters) between 13 and 40 weeks of gestation. Radiological scanning stage was carried out on 40 spontaneously aborted fetuses (19 males and 21 females) (12 second trimesters and 28 third trimesters) with multi-detector computed tomography. METHODOLOGY: One hundred and sixty nasal cavities and related structures were examined by means of bilateral dissection. Reference images were obtained in the axial plane with 3-mm collimation using multi-detector computed tomography (MDCT; Sensation 64, Siemens, Erlangen, Germany). These reference images were sent to the workstation (Leonardo, Siemens, Germany) and three-dimensional (axial, sagittal, and coronal) reformatted images with 1mm thickness were obtained via multiplanar imaging method. RESULTS: In the dissected fetuses 16 suprema nasal conchae were determined. Six (15%) NSDs (four towards the left and two towards the right) were detected on radiological sections. The angle between the virtual line from sphenoidal sinus ostium through limen nasi and the horizontal plane was 32.72+/-3.3 degrees on average. CONCLUSION: It was thought that some anatomic variations (e.g. suprema nasal concha, nasal septum deviation) occur in the fetal period; however, other certain differences (e.g. Onodi, Haller, and Agger nasi cells, concha bullosa) might be with effects of environmental factors (trauma and chronic infections) in postnatal period.

Developmental oronasal fistula of the incisive papilla.

Various terms (including patent nasopalatine fistula and patent nasopalatine duct) have been used to describe the presence of a developmental fistulous tract that connects the oral and nasal cavities through an oral opening located at the incisive papilla. Reportedly, this condition is a rare developmental variant; approximately 40 cases have been reported in the literature. Because awareness of this entity is important to avoid misdiagnosis, this article presents the clinical and conebeam computed tomography findings of two cases. Based on a review of the development of the nasopalatine structures in man, the authors propose that this entity be classified as a developmental oronasal fistula of the incisive papilla.

Nasal, septal, and turbinate anatomy and embryology.

This article discusses the development and anatomy of the nasal septum and structures of the lateral nasal wall. Emphasis is placed on anatomic variations associated with surgically correctable nasal obstruction. Common variations, such as deviated nasal septum, inferior turbinate hypertrophy, paradoxic middle turbinate, and concha bullosa, are discussed. Rare developmental causes of nasal obstruction are briefly outlined.

Supernumerary nostril: a case report and review / Fosa nasal supernumeraria: reporte de un caso y revisión

Supernumerary nostril is a very rare congenital anomaly, which includes additional nostril with or without accessory cartilage. In the present case of the left supernumerary nostril, a small cavity of around 3 mm diameter and accessory lower lateral cartilage were present. The cavity was lined with mucous membrane and filled with mucoid discharge .Nasal endoscopy of accessory nasal cavity revealed that it was small as compared to normal nasal cavity and did not communicate with the ipsilateral nasal cavity. The diameter of the normal anterior nasal opening was less on left side as compared to right side. Unilateral supernumerary nostril may occur because of the Assuring of the lateral nasal process during fetal growth.

Fosa nasal supernumeraria es una anomalía congénita muy poco frecuente, que incluye una nueva fosa nasal con o sin cartílago accesorio. En el presente caso de fosa nasal supernumeraria izquierda estaban presentes, una pequeña cavidad de unos 3 mm de diámetro y cartílago lateral accesorio inferior. La cavidad estaba revestida con membranas mucosas y llena con descarga mucoide. La endoscopía nasal de la cavidad nasal accesoria reveló que ésta era pequeña en comparación con la cavidad nasal normal y que no se comunicaba con la cavidad nasal ipsilateral. El diámetro normal de la apertura nasal anterior fue menor en el lado izquierdo en comparación con el lado derecho. La fosa nasal unilateral supernumeraria puede ocurrir a causa de las fisuras del proceso lateral nasal durante el crecimiento fetal.

Is the conduct of serres an anatomical variation in adults? / ¿Es el conducto de serres una variación anatómica en adultos?

In 1817, the denominated conduct of Serres was described as a formation that was highly prevalent in children's jaws, but considered as an anatomical variation in adults. In this study we analyze the presence of the denominated Serres'- conduct in 324 jaws belonging to the collection of the Universidade Federal de Sao Paulo (UNIFESP), with sex and age registration, 68 subadults of age between 0 and 2 years and 256 adults of age between 18 and 100 years. We found that the prevalence was in order to 100 percent in the subadults group and 42.6 percent in the adults group. In adults, the prevalence of this anatomical structure was greater in women than in men, with a difference statistically significant for the variable sex (Chi2 = 0.0148; I.C 95 percent=0.29-0.91; O.R. =0.51). According to the age, the biggest prevalence was in the fourth decade of the life, not being of any statistical significance for this variable. Based on the opposing evidence, this article discusses the character of anatomical variation of this formation and based on the anatomical terminology, intending to denominate the paramandibular canal.

El denominado conducto de Serres es una formación descrita en 1817, como altamente prevalente en mandíbulas de niños, pero considerado una variación anatómica en adultos. En este estudio analizamos la presencia del denominado conducto de Serres en 324 mandíbulas pertenecientes a la colección de la Universidade Federal de Sao Paulo, con registro de sexo y edad, 68 de subadultos de entre 0 y 2 años y 256 de adultos de entre 18 y 100 años. Nosotros encontramos un 100 por ciento de prevalencia en el grupo de subadultos y un 42.6 por ciento en el grupo de adultos. En adultos, la prevalencia de esta estructura anatómica fue mayor en mujeres que en hombres, con una diferencia estadísticamente significativa para la variable sexo (Chi²= 0.0148; I.C 95 por ciento=0.29-0.91; O.R.=0.51). De acuerdo a la edad, la mayor prevalencia se encontró en la 4ª década de la vida, no encontrándose significancia estadística para esta variable. En base a la evidencia encontrada, en este artículo se discute el carácter de variación anatómica de esta formación y basado en la terminología anatómica se propone denominarla canal paramandibular.

In vivo study of apoptosis as a creative agent of embryonic development of the primary nasal duct in rats.

INTRODUCTION: The first embryonic part of the nasal cavity is the primary nasal duct, beginning with the olfactory placode and ending with the oronasal membrane. Aim of this study was to investigate the cellular processes (apoptosis, proliferation) being responsible for development and opening of the primary nasal duct. MATERIAL AND METHODS: In this study developmental processes in at least three regions of the primary nasal duct (opening, middle, end) were examined by sectioning 38 rat fetuses on day 13.5 after conception. Apoptotic cells were detected by active caspase-3 antibodies and proliferating cells were examined by Ki-67 antibodies. RESULTS: Multiple apoptotic events were diagnosed on the basis and proliferative cells on the top of this duct. CONCLUSION: Apoptosis and proliferation play an important role in the process of opening the bottom of the primary nasal duct and for development of the nasal septum, philtrum as well as the primary palate. Mesenchymal proliferation seems to play a minor role in the process of opening the primary nasal duct.

Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development.

The Drosophila transcription factor Grainyhead (grh) is expressed in ectoderm-derived tissues where it regulates several key developmental events including cuticle formation, tracheal elongation and dorsal closure. Our laboratory has recently identified three novel mammalian homologues of the grh gene, Grainyhead-like 1, -2 and -3 (Grhl1-3) that rewrite the phylogeny of this family. Using gene targeting in mice, we have shown that Grhl3 is essential for neural tube closure, skin barrier formation and wound healing. Despite their extensive sequence homology, Grhl1 and Grhl2 are unable to compensate for loss of Grhl3 in these developmental processes. To explore this lack of redundancy, and to gain further insights into the functions of this gene family in mammalian development we have performed an extensive in situ hybridisation analysis. We demonstrate that, although all three Grhl genes are highly expressed in the developing epidermis, they display subtle differences in the timing and level of expression. Surprisingly, we also demonstrate differential expression patterns in non-ectoderm-derived tissues, including the heart, the lung, and the metanephric kidney. These findings expand our understanding of the unique role of Grhl3 in neurulation and epidermal morphogenesis, and provide a focus for further functional analysis of the Grhl genes during mouse embryogenesis.