Cartilaginous Nasal Capsule Research Articles

PECULIARITIES OF DEVELOPMENT OF THE HUMAN FACIAL REGION OF SKULL

PECULIARITIES OF DEVELOPMENT OF THE HUMAN FACIAL REGION OF SKULL

Ontogenetic transformation of the cartilaginous nasal capsule in mammals, a review with new observations on bats.

The nasal capsule, as the most rostral part of the chondrocranium, is a critical point of connection with the facial skeleton. Its fate may influence facial form, and the varied fates of cartilage may be a vehicle contributing to morphological diversity. Here, we review ontogenetic changes in the cartilaginous nasal capsule of mammals, and make new observations on perinatal specimens of two chiropteran species of different suborders. Our observations reveal some commonalities between Rousettus leschenaultii and Desmodus rotundus, such as perinatal ossification of the first ethmoturbinal. However, in Rousettus, ossification of turbinals is demonstrated as either perichondrial or endochondral. In Desmodus, perichondrial and endochondral ossification of the posterior nasal cupula is observed at birth, a part of the nasal capsule previously shown to persist as cartilage into infancy in Rousettus. Combined with prior findings on cranial cartilages we identify several diverse transformational mechanisms by which cartilage as a tissue type may contribute to morphological diversity of the cranium. First, cartilage differentiates in an iterative fashion to increase nasal complexity, but still retains the capacity for later elaboration via de novo bone emanating outward before or after cartilage ossifies. Second, cartilage acts as a driver of growth at growth centers, or via interstitial growth (e.g., septal cartilage). Finally, cartilage as a tissue may influence the timing of ossification and union of the facial and basicranial skeleton. In particular, cartilage at certain points of ontogeny may "model" via selective resorption, showing some similarity to bone.

Cephalic salt gland evolution in Mesozoic pelagic crocodylomorphs

Abstract Secondarily marine tetrapod lineages have independently evolved osmoregulatory adaptations for life in salt water but inferring physiological changes in extinct marine tetrapods is difficult. The Mesozoic crocodylomorph clade Thalattosuchia is unique in having both direct evidence from natural endocasts and several proposed osteological correlates for salt exocrine glands. Here, we investigate salt gland evolution in thalattosuchians by creating endocranial reconstructions from CT scans of eight taxa (one basal thalattosuchian, one teleosauroid, two basal metriorhynchoids and four metriorhynchids) and four outgroups (three extant crocodylians and the basal crocodyliform Protosuchus) to identify salt gland osteological correlates. All metriorhynchoids show dorsolateral nasal cavity expansions corresponding to the location of nasal salt glands in natural casts, but smaller expansions in teleosauroids correspond more with the cartilaginous nasal capsule. The different sizes of these expansions suggest the following evolutionary sequence: (1) plesiomorphically small glands present in semi-aquatic teleosauroids draining through the nasal vestibule; (2) moderately sized glands in the basalmost metriorhynchoid Pelagosaurus; and (3) hypertrophied glands in the clade comprising Eoneustes and metriorhynchids, with a pre-orbital fenestra providing a novel exit for salt drainage. The large gland size inferred from basal metriorhynchoids indicates advanced osmoregulation occurred while metriorhynchoids were semi-aquatic. This pattern does not precisely fit into current models of physiological evolution in marine tetrapods and suggests a unique sequence of changes as thalattosuchians transitioned from land to sea.

Resolving complex cartilage structures in developmental biology via deep learning-based automatic segmentation of X-ray computed microtomography images

The complex shape of embryonic cartilage represents a true challenge for phenotyping and basic understanding of skeletal development. X-ray computed microtomography (μCT) enables inspecting relevant tissues in all three dimensions; however, most 3D models are still created by manual segmentation, which is a time-consuming and tedious task. In this work, we utilised a convolutional neural network (CNN) to automatically segment the most complex cartilaginous system represented by the developing nasal capsule. The main challenges of this task stem from the large size of the image data (over a thousand pixels in each dimension) and a relatively small training database, including genetically modified mouse embryos, where the phenotype of the analysed structures differs from the norm. We propose a CNN-based segmentation model optimised for the large image size that we trained using a unique manually annotated database. The segmentation model was able to segment the cartilaginous nasal capsule with a median accuracy of 84.44% (Dice coefficient). The time necessary for segmentation of new samples shortened from approximately 8 h needed for manual segmentation to mere 130 s per sample. This will greatly accelerate the throughput of μCT analysis of cartilaginous skeletal elements in animal models of developmental diseases.

Inward collapse of the nasal cavity: Perinatal consolidation of the midface and cranial base in primates.

Living primates show a complex trend in reduction of nasal cavity spaces and structures due to moderate to severe constraint on interorbital breadth. Here we describe the ontogeny of the posterior end of the primate cartilaginous nasal capsule, the thimble shaped posterior nasal cupula (PNC), which surrounds the hind end of the olfactory region. We used a histologically sectioned sample of strepsirrhine primates and two non-primates (Tupaia belangeri, Rousettus leschenaulti), and histochemical and immunohistochemical methods to study the PNC in a perinatal sample. At birth, most strepsirrhines possess only fragments of PNC, and these lack a perichondrium. Fetal specimens of several species reveal a more complete PNC, but the cartilage exhibits uneven or weak reactivity to type II collagen antibodies. Moreover, there is relatively less matrix than in the septal cartilage, resulting in clustering of chondrocytes, some of which are in direct contact with adjacent connective tissues. In one primate (Varecia spp.) and both non-primates, the PNC has a perichondrium at birth. In older, infant Varecia and Rousettus, the perichondrium of the PNC is absent, and PNC fragmentation at its posterior pole has occurred in the former. Loss of the perichondrium for the PNC appears to precede resorption of the posterior end of the nasal capsule. These results suggest that the consolidation of the basicranial and facial skeletons happens ontogenetically earlier in primates than other mammals. We hypothesize that early loss of cartilage at the sphenoethmoidal articulation limits chondral mechanisms for nasal complexity, such as interstitial expansion or endochondral ossification.

Ontogeny and phylogeny of the mammalian chondrocranium: the cupula nasi anterior and associated structures of the anterior head region

BackgroundThe study of chondrocrania has a long tradition with a focus on single specimens and stages. It revealed great interspecific diversity and a notion of intraspecific variation. As an embryonic structure, the chondrocranium is subject to major changes in ontogeny with resorption and ossification of different cartilaginous structures. The cupula nasi anterior is the anteriormost portion of the cartilaginous nasal capsule and is expected to mirror much of the animal's life history and lifestyle. Its diversity in mammals is reflected in the external nasal anatomy of newborns. Marsupials and placentals show marked differences, likely related to breathing and suckling behavior.ResultsWe examined histological sections of five marsupial and three placentals species and traced the development of the cupula nasi anterior and the anterior nasal capsule. We found ontogenetic variation for nearly 50% of the 43 characters defined herein. By comparing to the literature and considering ontogenetic variation, we performed an analysis of character evolution in 70 mammalian species and reconstructed the nasal anatomy of the therian ancestor.ConclusionsAt birth, marsupials have a complete but simple cupula nasi anterior, whereas placentals display a more diverse morphology due to reductions and variations of chondrocranial elements. The more compact nasal capsule in marsupials is related to a long and strong fixation to the mother’s teat after birth. Within marsupials and placentals, several derived characters distinguish major taxa, probably related to developmental and functional constraints. The reconstructed ancestral anatomy of the cupula nasi anterior supports the hypothesis that the therian ancestor was placental-like and that the marsupial lifestyle is more derived.

Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage.

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.

Comparative morphogenesis of nasal region in human and some mammals.

Background . Comparative anatomical and embryological research has not lost its relevance in the wide field of human body structures and systems studying. Analysis of current scientific literature concludes that the problem of prenatal morphogenesis of the nasal cavity structures in comparative embryological aspect still remains unsolved. Objective . The aim of the study was to clarify specific structural features of nasal region structures during prenatal morphogenesis in human and some mammals. Materials and methods. Research was conducted on 75 specimens of human fetuses and embryos and 85 mammals’ specimens in different periods of prenatal development by using complex of morphological methods (anthropometry, morphometrics, microscopy, three-dimensional computer reconstruction and statistical analysis). Results . At the end of the fetal period of ontogenesis, nasal region in studied mammalian species acquires features of a definitive structure. It is surrounded by cartilaginous nasal capsule, to the exterior surface of which are adjacent dorsally - nasal and partly frontal bones, lateral - maxillary bones. Nasal cavity is delimited from the cranial cavity by cribriform plate of sphenoid, which consists of cartilage. Nasal cavity is divided into two halves by cartilaginous nasal septum, which aborally proceeds into cartilaginous skull base, dorsally – into the vault of nasal capsule. Ventral wall of nasal cavity consists of paraseptal cartilages and secondary bone palate. Conclusions . It was found that differences of nasal region structure in studied mammals were associated with form of nasal cavity, structure of secondary palate bone, number and developmental degree of nasal cavities and paranasal sinuses. This differences are caused by nutrition features, nature of dental armament, degree of brain development, intensity of respiration and animals’ conditions of existence. In humans lateral nasal gland is absent, however respiratory, olfactory and maxillary glands are well developed.

Nasal anatomy of the non-mammaliaform cynodont Brasilitherium riograndensis (Eucynodontia, Therapsida) reveals new insight into mammalian evolution.

The mammalian nasal cavity is characterized by a unique anatomy with complex internal features. The evolution of turbinals was correlated with endothermic and macrosmatic adaptations in therapsids and in early mammals, which is still apparent in their twofold function (warming and moistening of air, olfaction). Fossil evidence for the transformation from the nonmammalian to the mammalian nasal cavity pattern has been poor and inadequate. Ossification of the cartilaginous nasal capsule and turbinals seems to be a feature that occurred only very late in synapsid evolution but delicate ethmoidal bones are rarely preserved. Here we provide the first µCT investigation of the nasal cavity of the advanced non-mammaliaform cynodont Brasilitherium riograndensis from the Late Triassic of Southern Brazil, a member of the sister-group of mammaliaforms, in order to elucidate a critical anatomical transition in early mammalian evolution. Brasilitherium riograndensis already had at least partially ossified turbinals as remnants of the nasoturbinal and the first ethmoturbinal are preserved. The posterior nasal septum is partly ossified and contributes to a mesethmoid. The nasal cavity is posteriorly expanded and forms a distinctive pars posterior (ethmoidal recess) that is ventrally separated from the nasopharyngeal duct by a distinct lamina terminalis. Thus, our observations clearly demonstrate that principal features of the mammalian nasal cavity were already present in the sister-group of mammaliaforms.

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.

Cranial osteology of Exostinus serratus (Squamata: Anguimorpha), fossil sister taxon to the enigmatic clade Xenosaurus

Within the squamate clade Anguimorpha, Xenosaurus is an enigmatic taxon combining several apparently primitive features with a highly specialized set of autapomorphies. This combination makes the fossil record along the Xenosaurus stem particularly important for resolving the relationships of Xenosaurus with other anguimorphs, and between species of Xenosaurus.Exostinus serratus Cope, 1873 from the Oligocene of the western United States is currently hypothesized to be the immediate sister taxon to Xenosaurus. The cranial osteology of this pivotal taxon is described here for the first time from all known material, using high-resolution X-ray computerized tomography (CT) scanning to visualize individual elements. Exostinus serratus displays a mosaic of ancestral anguimorph features that are transformed in Xenosaurus, as well as unique synapomorphies shared with Xenosaurus. The region of the external nares is less transformed than in Xenosaurus, as are the general proportions of the bones surrounding the cartilaginous nasal capsule. However, the forms of the teeth and of the osteodermal sculpture, as well as several details of maxillary and mandibular morphology, are distinctly Xenosaurus-like. Several autapomorphies are also present, including an abbreviated tooth row and an unusually wide palatal shelf of the maxilla. An understanding of the ways in which the non-ossified tissues of the head influenced the development of the bones is crucial to interpreting their morphology. Furthermore, subtle anatomical features often provide important comparative information, and are emphasized herein. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 159, 921–953.

The nasal capsule of platyrrhine primates in relation to paranasal pneumatization

Recent work posits that “true” paranasal sinuses form by an invasive process that is distinct from general bone remodeling. One hypothesis holds that breakdown of the cartilaginous nasal capsule that surrounds recesses is a necessary prelude to secondary pneumatization. To test this hypothesis, we examined heads of perinatal New World primates (n = 9) that were serially sectioned in the coronal plane. In two species that form frontal sinuses that derive from the frontal recess, the lateral wall of the nasal capsule (paries nasi) is relatively less extensive compared to three species in which no frontal sinus forms from this recess. A single species in our sample (Saimiri sciureus) does not form a maxillary sinus. This species is distinguished by the presence of extensive remnants of the inferior margin of the paries nasi. More generally, in species with postnatal maxillary or frontal sinuses, the nasal capsule along the wall of the maxillary or frontal recesses is more fragmented. These findings support the hypothesis that nasal capsule breakdown is a crucial event preceding sinus formation. These findings also suggest that absence of “true” sinuses may correlate with protracted perinatal presence of capsular cartilage surrounding the natal recess.

Ontogeny and homology of the paranasal sinuses in Platyrrhini (Mammalia: Primates)

The identity and taxonomic distribution of paranasal sinuses among living platyrrhines has remained a contentious issue (e.g., Cave [1967] Am J Phys Anthropol 26:277-288 vs. Hershkovitz [1977] Chicago: University of Chicago Press) largely because the ontogenetic data required for their detection and identification (e.g., Cave [1967]; Maier [2000] Cambridge, UK: Cambridge University Press, 99-132.) were not attainable without sacrificing valuable juvenile and subadult specimens. Non-invasive computed tomography (CT) scanning of ontogenetic series of skulls for 10 platyrrhine genera demonstrates the presence of maxillary and ethmoid sinuses, as well as homologs of the human sphenoid and frontal sinuses. Differences in the latter two sinuses between platyrrhines and hominoids highlight the need for early developmental data in establishing sinus homology. In particular, the identification of homologous recesses in the cartilaginous nasal capsule, from which sinuses later develop, emerges as the critical step. This developmental approach also reveals that the anterior and posterior ethmoid sinuses are each sets of serial homologs, a point which reconciles previous difficulties in establishing sinus homologies across mammalian orders (e.g., Paulli [1900] Gegenbaurs Morphol Jahrb 28:147-178, 179-251, 483-564).

Early development of the nose in human embryos: a stereomicroscopic and histologic analysis.

To analyze the morphologic features of the nose in the human embryo from the 4th to 8th developmental week according to Carnegie stage. Stereomicroscopic and histologic analysis of the morphology of the human embryo. A total of 27 cases of embryos, ranging from Carnegie stage 13 to 23, were analyzed. The external morphology was observed with a stereomicroscope, photographed, and analyzed. The histologic features were observed with a light microscope in the horizontally transected specimens stained with hematoxylin-eosin. The nasal placode was observed in stage 13, and it became flat or even concave in stage 14. In stage 15, the nasal pit was formed. In stage 16, the nasal sac and nasal fin were observed. In stage 17, the oronasal membrane was formed by thinning of the nasal fin. In stage 18, the primitive choana was established by a rupture of the oronasal membrane. In stage 19, the lateral palatine process projected vertically below the level of the tongue. The cartilaginous nasal capsule was formed in stage 20. In stage 21, the olfactory area was localized to the upper portion of the lateral nasal wall and the nasal septum. In stage 22, the lateral palatine process developed in a somewhat horizontal orientation. In stage 23, the premaxilla and primitive choana were formed. The development of the nose is most active from Carnegie stage 13 to 19, which corresponds to the end of the fourth embryonic week to the end of the seventh week. Thus, this period is considered to be the most important period in human nasal embryonic development.

Chondrogenic differentiation during midfacial development in the mouse: in vivo and in vitro studies

Because the mouse is now the main model for developmental research of all types, it is important to understand the basic developmental pattern of various organs. The first aim of the present study was to establish normal prenatal developmental standards of the cartilaginous nasal capsule during embryonic development of the mouse. For this purpose we have performed sagittal and coronal sections ranging from E12.5 to E18.5 in gestation age. The primordia of the nasal septal cartilage is recognizable around the 14th embryonic day as demonstrated by the metachromatic toluidine blue staining and by immunostaining of type II collagen. Northern blot analysis of the transcription factors Cart-1 and Sox-9 indicated maximum mRNA levels at E12.5 then a decreased expression during the following days of gestation. Type II collagen and aggrecan mRNA levels are constant during the embryonic period. In the second part of this study, we have established a primary culture system where chondrocytes were isolated from E.18 mouse embryo nasal septum. The purpose of this second part was to assess if chondrocytes could further differentiate in vitro until the hypertrophic phase and matrix mineralization. After the condensation phase, the cells synthesize an extracellular matrix including type II collagen and aggrecan. Progressively, typical cartilaginous nodules composed of clusters of round cells are visible, then increase in size and finally mineralize at day 12 of culture. Cart-1 and Sox-9 mRNA levels remain constant throughout the cultures, whereas type II collagen and aggrecan gradually decrease. Ultrastructural observations of the nodules show typical chondrocytes embedded in a dense network of fibers with matrix vesicles and mineralized foci. Other ultrathin sections revealed the presence of chondrons, typical of hyaline cartilage. Results from this study provide useful tools to further investigate morphogenesis and differentiation of the cartilaginous nasal capsule, and could in the future serve as a basic developmental standard.

Morphology of the nasal capsule of Heloderma suspectum with comments on the systematic position of helodermatids (Squamata: Helodermatidae)

A serially sectioned embryonic head of Heloderma suspectum formed the basis for a three‐dimensional reconstruction of the cartilaginous nasal capsule and its membrane bones. Further, the soft parts of the nasal capsule were analysed microscopically. The embryonic nasal capsule is described and compared to the morphological conditions in other lizards, especially the varanids, which many recent authors believe to be their closest relatives.The results support the close affinities between the helodermatids and the varanids. Both groups have a well developed recessus lateralis in a cartilaginous capsule, entered by the nasal concha. Further, in both groups a fragmentation of the cartilago paraseptalis occurs in a comparable location and form. Heloderma has no double lacrimal duct, in contrast to previous accounts, but the two canaliculi at the origin of the duct fuse noteworthy far ahead (in other squamates they fuse in front of the bulbus oculi). In the varanids the two branches of the lacrimal duct remain separate and open separately.Some unique features of Heloderma are presented as well, above all the presence of a second concha.

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.

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.

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. (Otolaryngol Head Neck Surg 1996;114:54-60.)

Craniofacial Dysmorphia of Frontal Proboscis in Holoprosencephaly

ABSTRACTWe have examined eleven cases of holoprosencephaly with special emphasis on the frontal proboscis. Although the nostril appears blind ended grossly, the proboscis has a single slender midline nostril lined with squamous mucosa containing numerous sebaceous glands. It is actually connected to a poorly formed but definite nasal cavity microscopically. The inner portion of the nostril tunnel is lined by olfactory mucosa containing numerous subjacent secretary glands. Despite the absence of olfactory bulbs and tracts the cartilaginous nasal capsule is identified along with abnormal nasal cavity. However, the nasal capsule is hypoplastic, and has an aberrant nasal septum and no concha. In severe form of holoprosencephaly, i.e., cyclopia, the nasal capsule is noted above the level of the ethmoid plate, in which case the nasal cavity dose not communicate with nasopharynx because it is too distant from the hypoplastic maxilla. Therefore, choanal atresia is resulted. Although unique maxillary bone comprises the whole upper jaw, the failure of fusion between vomeronasal septum and palatal processes in holoprosencephaly results in abnormal maxillary bone which is characterized by a narrow palate without palatal arch form. Nevertheless, through serial microscopic sections we could find a space between the posterior maxilla and the sphenoid bone, which is composed of adipose tissue and is similar in shape to the nasal capsule. This space is thought to be made for the nasal capsule during early developmental period. The present study suggests that the frontal proboscis in holoprosencephaly is an undescended nose. In most cases it is connected to the aberrant nasal cavity which is located beneath the proboscis. The level of proboscis descends gradually toward normal nose position as the severity of holoprosencephaly decreased from cyclopia, ethmocephaly, cebocephaly, to premaxillary agenesis. Key words: frontal proboscis, holoprosencephaly, craniofacial dysmorphia