The juxta-oral organ of Chievitz (organum yuxtaorale) updated: Embryology, anatomy, function and pathology.

BACKGROUND: The Chievitz's organ or juxta-oral organ is a mysterious bilateral structure, phylogenetically preserved, which develops from the mouth epithelium as an invagination that loses connection to it in the prenatal period. It is located laterally to the walls of the oral cavity in an imprecise anatomical location and receives abundant innervation from the buccal nerve. Structurally it consists of non-keratinizing squamous-like neuroepithelial cells surrounded by two layers of connective tissue with nerve fibers and different morphotypes of sensory corpuscles. Its function is completely unknown although based on its rich innervation it is assumed that works as a mechanoreceptor. METHODS: We have performed immunohistochemistry for axonal and Schwann cells, and the putative mechanoproteins ASIC2, TRPV4 and Piezo2 in sections of fetal juxta-oral organ. RESULTS: Intraparenchymatous nerve fibers and sensory corpuscles were observed as well as immunoreactivity for Piezo2 in both nerve fibers and epithelial parenchymatous cells. CONCLUSIONS: We add indirect evidence that the juxtaoral organ is a mechanoreceptor because in addition to its dense innervation, the epithelial cells and sensory nerve fibers display immunoreactivity for the mechanogated ion channel Piezo2. Based on current knowledge, the functional and clinical importance of the juxta-oral organ should be further investigated.

Chievitz' juxtaparotid organ, free from cancer.

INTRODUCTION: Up to the half of twentieth century, Chievitz organ was considered an embryonal organ, disappearing with growth. But Zenker, in 1953, demonstrated the existence of this organ in adult life, too4. REVIEW: In this article we review the embryology, the macroscopic and microscopic anatomy, the ultrastructure, the functional significance and the pathology of the Chievitz'Juxtaparotid Organ (CJO). The CJO is not a macroscopic apparent organ, but it looks like a nerve. The CJO takes connections with buccinator muscle, at the level of the parotid duct, and the medial pterygoid muscle. The cell parenchyma is enveloped by the connective tissue, that is divided into three layers15, 16: the inner layer -"stratum fibrosum internum"-, composed of collagenous and elastic microfibrils; the middle layer - "stratum nervosum" - containing a lamellar inner core and Ruffini SNF5; the external layer - "stratum fibrosum externum", that is a collagen capsule. The parenchymal cells show a rich enzyme activity. The parenchymal cells may play the same role as glomus cells of the 1st type and Merkel cells20, 21. When a surgical resection is performed for an oral carcinoma, the CJO may be present in the specimen25. The CJO may be wrongly diagnosed as perineural invasion by carcinoma26, 27, 28. CONCLUSION: We report that Chievitz' organ is the only organ in which the cancer does not occur. KEY WORDS: Chievitz' organ, Juxtaoral organ, Parotid gland.

Organogenesis of the juxta-oral organ in mice.

The juxta-oral organ is a bilateral organ in the mammalian bucca. It consists of epithelial cords with surrounding mesenchyme. It develops from embryonic oral epithelium, but its macroscopic morphology in mice is less studied and seems to be very different from that of humans. The juxta-oral organ in mice extends more widely from the subcutaneous tissue of the mandible near the lateral fascia of the masseter to the submucosa of the soft palate. In this paper, we report that the mutant mouse allele Bmp7(lacZ) presented intense lacZ expression in the epithelial component of the juxta-oral organ in its homo- and heterozygous states. The main aims of this study were to show that this mutant mouse allele is suitable for observing macroscopic structure of the juxta-oral organ and to describe the development of this organ during embryonic and postnatal stages. Whole-mount beta-gal staining of this strain of mouse showed that the juxta-oral organ in mice appeared at E12.0 from oral epithelium and lost connection with it before E12.5. Then, the juxta-oral organ extended anteriorly to the lateral fascia of the masseter and posteriorly to the submucosal layer of the soft palate via the orbit. The mature juxta-oral organ had no connection to other epithelia such as those of the bucca and parotid duct. It persisted until adulthood and there seemed to be no tendency to regress. Transmission electron microscopy showed that each part of the juxta-oral organ was an epithelial cord surrounded by a basement membrane and mesenchymal tissue.

[Juxtaoral organ of Chievitz].

This review presents the analysis of the systematized data on human juxtaoral organ (JOO) development, structure and function based on the results of classical and recent morphological studies. JOO morphogenesis is traced, including the appearance of its anlage at the bottom of the primitive mouth, epithelial invagination into the mesenchyme, JOO detachment from the oral epithelium, its innervation, connective tissue capsule formation, and final maturation. The analysis of the results of macroscopical, histological, electron microscopical, histochemical and immunohistochemical studies is presented, suggesting high metabolic and synthetic activity of its epithelium, which expresses several neural markers, and emphasizing a rich innervation of both its epithelial and stromal components. The findings supporting the concepts of JOO secretory and mechanosensory functions, are examined. The data on the differential diagnosis between JOO and tumoral processes are discussed, as well as the pathological changes of JOO itself and their significance for the diagnosis of the diseases.

Apoptosis as a creative agent of embryonic development of bucca, mentum and nasolacrimal duct. An in vivo study in rats.

INTRODUCTION: For embryonal facial development several fusion processes between different facial prominences are necessary. If fusion fails to appear, various facial clefts may occur, known as median (e.g. lower median cleft lip), oblique (e.g. open nasolacrimal duct) or lateral facial clefts (macrostomia, lateral cleft). MATERIAL AND METHODS: The development of 3 different facial regions (bucca, mentum, and nasolacrimal duct) was examined in rats using serial histological sections on day 13.5 after conception. Common procedures were used (staining for active caspase-3 and for Ki-67) for histological assessment about the role of apoptotic and proliferative processes in the fusion zones of buccal, mental and nasolacrimal areas. RESULTS: Multiple apoptotic events were detected in epithelial cells of the respective regions, the proliferative centers were located in the mesenchymal surroundings of fusion zones. CONCLUSION: A substantial precondition for fusion of facial prominences are proliferative and apoptotic processes in epithelial and mesenchymal cells. Apoptosis contributes to the development of bucca, mentum and the nasolacrimal duct. Absence of apoptoses may be responsible for facial clefts.

Fetal cheek-to-cheek diameter in the prediction of mode of delivery.

OBJECTIVE: The purpose of this study was to assess sonographic fetal cheek-to-cheek diameter (CCD) in predicting mode of delivery. STUDY DESIGN: Two hundred sixty-four patients were considered in 2 parts. First, a retrospective analysis of 214 patients entered into a birth weight (BW) study. Measurements of the CCD, biparietal diameter (BPD), and BW, as well as labor data, were collected. Then a prospective study of patients at > or =38 weeks gestational age was conducted. Fetal weight (EFW) was estimated by routine measurements. Information regarding CCD was withheld from the delivering caregiver. Labor records were reviewed for BW and complications, defined as: instrumental delivery, cesarean section (C/S) for nonprogress of labor or "CPD," and "difficult" vaginal delivery. The CCD, BW (both parts), or EFW (prospective part) and mode of delivery were compared. RESULTS: Abnormal CCD (>2SD above previously published norms for each GA) was closely associated with cesarean delivery, regardless of EFW. At term, risk of C/S with a CCD >7.9 cm was 94%. CONCLUSION: Within limits, EFW alone has weak correlation with cesarean delivery. CCD, as a reflector of fetal adipose tissue, performs as well as actual BW and demonstrates good prediction for delivery by C/S.

Increased apoptosis during morphogenesis of the lower cheek teeth in tabby/EDA mice.

In wild-type (WT) mice, epithelial apoptosis is involved in reducing the embryonic tooth number and the mesial delimitation of the first molar. We investigated whether apoptosis could also be involved in the reduction of tooth number and the determination of anomalous tooth boundaries in tabby (Ta)/EDA mice. Using serial histological sections and computer-aided 3D reconstructions, we investigated epithelial apoptosis in the lower cheek dentition at embryonic days 14.5-17.5. In comparison with WT mice, apoptosis was increased mainly mesially in Ta dental epithelium from day 15.5. This apoptosis showed a similar mesio-distal extent in all 5 morphotypes (Ia,b,c and IIa,b) of Ta dentition and eliminated the first cheek tooth in morphotypes IIa,b. Apoptosis did not appear to play any causal role in positioning inter-dental gaps. Analysis of the present data suggests that the increased apoptosis in Ta mice is a consequence of impaired tooth development caused by a defect in segmentation of dental epithelium.

Down syndrome: a study of chromosomal mosaicism.

Recent data suggest that chromosome mosaicism is a possible mechanism for intrauterine and postnatal survival in cases of trisomy 18 and Turner syndrome (45X). The aim of this study was to evaluate if chromosomal mosaicism is a possible mechanism of survival in Down syndrome (DS) (trisomy 21) individuals. Mosaicism was studied by interphase fluorescence in-situ hybridization (FISH), using a specific probe for chromosome 21 (21q22.13-21q22.2) in 78 cases suspected of DS. To rule out tissue specific mosaicism, buccal cells or amniocytes were analysed in addition to blood in 20 DS cases. Thirty-three per cent of the cases studied by FISH in only peripheral blood were mosaics. In 20 cases of trisomy 21, two tissues were studied and mosaicism was not detected in either of the two tissues in 15 cases. The remaining five cases were mosaics in both the tissues analysed. Clinical comparisons in 17 DS mosaics showed a direct relationship between the percentage of trisomic cells and the degree of phenotypic manifestations. These results suggest that mechanism(s) other than mosaicism may exist for the intrauterine and postnatal survival of DS cases.

DNA fingerprinting of sister blastomeres from human IVF embryos.

BACKGROUND: Previously published single cell DNA fingerprinting systems have been plagued by high rates of allele drop-out (ADO) and preferential amplification (PA) preventing clinical application in preimplantation genetic diagnosis. METHODS: Tetranucleotide microsatellite markers with high heterozygosity, known allelic size ranges and minimal PCR stutter artefacts were selected for chromosomes X, 13, 18 and 21 and optimized in a multiplex fluorescent (FL)-PCR format. FL-PCR products were analysed using the ABI Prism 377 DNA sequenator and Genescan software. Validation of the DNA fingerprinting system was performed on single diploid (n = 50) and aneuploid (n = 25) buccal cells and embryonic blastomeres (n = 21). RESULTS: The optimized pentaplex PCR DNA fingerprinting system displayed a high proportion of successful amplifications (>91%) and low ADO and PA (<6%) when assessed on 50 human buccal cells. DNA fingerprints of single cells from a subject with Down's syndrome detected the expected tri-allelic pattern for the chromosome 21 marker, confirming trisomy 21. In a blind study on 21 single blastomeres, all embryos were identifiable by their unique DNA fingerprints and shared parental alleles. CONCLUSIONS: A highly specific multiplex FL-PCR based on the amplification of five highly polymorphic microsatellite markers was developed for single cells. This finding paves the way for the development of a more complex PCR DNA fingerprinting system to assess aneuploidy and single gene mutations in IVF embryos from couples at genetic risk.

The Chievitz juxtaparotid organ.

The Chievitz juxtaparotid organ represents a macroscopic longitudinal formation, which is developed from oral cavity ectoderm in its lateral wall. As to its function, the organ probably represents a mechanosensor with different qualities of perception. The information coming from its sensors takes part in different activities of the lateral wall of oral cavity during sucking, swallowing, mastication, speech, protecting reflexes and wall tonus. The Chievitz juxtaparotid organ is not only a morphologically interesting structure, but is of great importance also for clinic and surgical pathology of the oral cavity.

Incorporating sonographic cheek-to-cheek diameter, biparietal diameter and abdominal circumference improves weight estimation in the macrosomic fetus.

The objective of this study was to improve the accuracy of sonographic fetal weight estimation in macrosomic (> 4000 g) fetuses by combining the cheek-to-cheek diameter (CCD), an indicator of subcutaneous tissue mass, with the biparietal diameter (BPD) and abdominal circumference (AC) in generating a new weight formula. Three hundred well-dated, uncomplicated singleton pregnancies > 32 weeks' gestational age (GA) were analyzed. Sonographic fetal measurements obtained in every case included BPD, head circumference, AC, femur length and CCD. Sonographic estimation of fetal weight (EFW) was derived by using BPD and AC. Actual birth weights (BW) of fetuses delivered within 7 days of the last sonographic examination and weighing over 1500 g (n = 123) were compared to EFW. A formula was derived by correlating BPD, AC and CCD with BW in these 123 fetuses using multiple regression analysis. A second formula was derived from the data of 39 macrosomic fetuses. The two formulae were then tested for accuracy of prediction of fetal weight in 157 other fetuses delivered within 7 days and grouped by birth weight, 44 of them weighing > 4000 g. The new formula for macrosomic fetuses was: EFW (g) = 1065 + 84.5 BPD (cm) + 41.29 AC (cm) + 111.0 CCD (cm). In the macrosomic fetuses, a difference of < 10% between EFW and BW was demonstrated in 72.7% by the BPD-AC formula and 95.5% when incorporating CCD. In this group, the mean percentage error was significantly smaller: 4.14 vs. 7.97% (p = 0.0005). In the regression analysis, the contributions of BPD, AC and CCD to the variance in BW were 5.5%, 16%, and 18.3%, respectively (p = 0.008). In the non-macrosomic fetuses, CCD improved prediction of BW, but the trend did not reach statistical significance. Our results demonstrate that, in the macrosomic fetus, CCD explains more of the variance in BW than other parameters and incorporating it in the sonographic weight estimation greatly improves its accuracy.

[Histo-ontogenetic study of the major salivary glands and Chievitz's organ]. / Studio isto-ontogenetico sulle ghiandole salivari maggiori e dell'organo di Cheivitz.

Salivary glands development has been studied by optical microscopy in 8 fetuses aged from 8 to 20 weeks of fetal life. From the observation of the sections obtained we can assume that submandibular gland is the first gland to be detectable, later the parotid gland and then the sublingual gland. In tight connection with the parotid gland Chievitz organ has been demonstrated. It is not known whether this organ may or may not contribute to parotid gland.

[Development of the definite angle of the mouth in man]. / Die Bildung des definitven Mundwinkels beim Menschen.

Until today different views exist on the development of the cheek and the final angle of the mouth. Recently, new results have been found indicating a cialisation of the epithelium during the fusion or adhesion of prominences covered by epithelia. Our results led to further information on the development of the angle of the mouth. 23 human embryos and fetuses were studied by scanning electron microscopy. The transition zone between the maxillary swelling and the mandibular arch is characterized by numerous small surface cells with long stretched lamellopodia without forming a fusion zone. At stages 12-22 of human embryos the maxillary process grows first in a cranial direction, than towards ventral and medial. Thus, the angle of the mouth moves mediad, the oral opening is not reduced in size. A lack of full growth of the mandibular arch and the maxillary swelling causes macrostomia. The definite labial commissure is not due to a fusion of the maxillary and mandibular swellings.

Cancer of the cheek.

The combined skills of the micrographic surgeon and the head and neck surgeon offer excellent cure rates and reconstructive techniques for primary cutaneous tumors of the cheek. In most instances, structures crucial to facial function and appearance can be preserved or rehabilitated. This interspecialty approach to such tumors results in the best care for the patient and a high sense of professional satisfaction for the surgical team.

The use of retinoids as probes for analyzing morphogenesis of glands from epithelial tissues.

Thirty-five years ago Honor Fell and Edward Mellanby were studying effects of high doses of vitamin A on skeletal development in chick embryos when they noticed that a piece of epidermis, accidentally included in an organ culture, had undergone mucous metaplasia. Further studies by Fell and others eventually led to an understanding of the important role of vitamin A in modulating epithelia in vivo. Fifteen years later another organ culture experiment showed me that excess vitamin A could also initiate the morphogenesis of branching and mucus-secreting glands from developing vibrissa follicles in upper lip skin of embryonic mice. Since then our group has shown that induction of this novel structure by naturally occurring retinoids resembles a normal embryonic induction in that it is stage-dependent, time-dependent, and irreversible. Tissue separation and recombination studies showed that isolated upper lip epidermis can form these glands when combined with retinoid-treated upper lip dermis. Untreated mouse epidermis can form similar glands after combination with chick dermis containing higher retinoid levels. The hamster cheek pouch, normally devoid of glandular structures, can also form mucous glands when treated with a retinoid, either in vivo or in vitro. Recombination studies in organ culture have now shown that mesenchyme exposed to retinoid is essential for gland morphogenesis from pouch epithelium. Evidence is accumulating that retinoic acid may even be the active morphogen in some normally developing systems.

Morphological changes in the oral (buccopharyngeal) membrane in urodelan embryos: development of the mouth opening.

The ultrastructure of the oral (buccopharyngeal) membrane in the embryo of the urodelan, Hynobius tokyoensis, was examined by transmission (TEM) and scanning electron microscopy (SEM). The oral membrane consists of the stomodeal ectoderm and foregut endoderm, and is three to five cell layers thick at stage 24. The oral membrane gradually thickens as development proceeds. The stomodeal collar, derived from the ectoderm, is folded inward along the foregut endoderm. Tooth germs are formed partly by cells of the stomodeal collar and partly by mesenchymal cells and calcification takes place before hatching. Secretory granules, which are markers of epithelial differentiation, appear in some cells of the foregut endoderm. Within the oral membrane, the cells of the stomodeal collar become the basal cells, and the endodermal cells of the foregut become the apical cells of the future oral epithelium. Gaps are formed by the epithelial differentiation of the endodermal cells of the foregut in the oral membrane. The gaps connect with each other, with the stomodeum, and with the foregut. As a result of these events, the mouth opens at stage 43, just after hatching.

The development of the Syrian hamster cheek pouch.

The objective of this study was to provide a detailed account of the morphogenesis and early cytodifferentiation of the hamster cheek pouch. Although the newborn "cheek pouch" is used for in vitro studies of the effects of retinoids and carcinogens, its rudimentary structure has not been adequately described. Complete paraffin serial sections of the heads of 14- and 15-day fetuses were cut in three planes to determine the location and shape of the earliest pouch rudiments. Complete paraffin serial sections were prepared from pouch rudiments dissected from hamsters at birth and at daily intervals from 3 to 12 days postnatal. Semithin Epon sections were examined by light microscopy and ultrathin sections by transmission electron microscopy. The pouch can appear in the fetus as two solid epithelial ingrowths from the lining of the oral cavity. They are the margins of an ingrowing sheet of oral epithelium which becomes leaflike at about the time of birth, as it grows caudad into the tissue of the cheek. The central cells of the ingrowth accumulate large quantities of glycogen before differentiating as a stratum spinosum 5 days after birth. Within the stratum spinosum, groups of cells containing keratohyalin granules initiate the stratum granulosum. Keratinized cells appear within the stratum granulosum areas. Spaces appear between keratinized cells, and the spaces coalesce to form the pouch cavity between 7 and 12 days postnatal. Soon afterward, this cavity opens to the oral cavity to make a pouch, and the ultrastructure of the cheek pouch epithelium closely resembles that of the adult.

Growth and development of human adipose tissue during early gestation.

805 normal-for-age human embryos and fetuses were used to study early prenatal fat development. The investigation included observations on stages of fat morphogenesis at the light microscopic level and computerized image analyses of fat lobule size and number. The buccal fat pad was selected as a model system for the analyses. Fat tissue differentiates between the 14th and the 16th weeks: there are five morphogenic phases in adipose tissue formation, strongly associated with the formation of blood vessels. Fat lobules are the earliest structures to be identified before typical vacuolated fat cells appear. Concerning fat lobule size and number, we show that after the 23rd week the total number of fat lobules remains approximately constant, while from the 23rd to 29th week the growth of adipose tissue is determined mainly by an increase in size of the lobules. These results suggest that the 14th through the 23rd week is a sensitive period in fat lobule development, and that disturbances of normal adipogenesis during this period may play a role in the etiology of obesity in later life.

Intra-uterine healing of fetal rat cheek wounds.

Cheek wounds, involving skin, mucosa, and muscle, were surgically created in utero on Sprague Dawley rat fetuses at 19 1/2 days gestation. Fifty fetuses were used in the study. Twenty-five fetuses were in the experimental group and 25 in the control. Five fetuses in each group were sacrificed at 0, 6, 12, 18 and 24 hours post-operatively. Serial histological sections in the coronal plane were stained with haematoxylin and eosin. Restoration of continuity and primary epithelialisation of the oral mucosal and skin surfaces of the wound was observed to occur within 24 hours. The continuity of the muscle layer was not restored, but some mitoses were seen in the myeloblasts. There was a complete absence of acute inflammatory cells, and there was no scab formation. Healing occurred without scarring. These findings are discussed in comparison to previous findings on orofacial fetal wound healing (Goss 1976) and in regard to future prospects in intraceptive fetal surgery for the correction of deformities, in particular cleft lip.

Subdivision of mouse vibrissae on an embryological basis, with descriptions of variations in the number and arrangement of sinus hairs and cortical barrels in BALB/c (nu/+; nude, nu/nu) and hairless (hr/hr) strains.

Development of vibrissae was studied in dd/y mouse embryos by scanning electron microscopy. Arrangement of vibrissae and cortical barrels were also studied by light microscopy in adult dd/y, BALB/c(nu/+), nude (BALB/c, nu/nu) and hairless (hr/hr) mice to find genetic or epigenetic variations. Rudiments of vibrissae first appear on Day 12 of pregnancy as longitudinal ridges on the developing muzzle, and each hair rudiment is represented by a dome on the ridges. The dorsal two rows (A and B; Woolsey and Van der Loos, '70) of mystacial vibrissae are on the lateral nasal prominence, while the ventral three (C, D and E) are on the maxillary prominence. Smaller hairs of mystacial vibrissae appear at the labial part of the maxillary prominenceon Day 13. The rudiments of rhinal hairs also appear at this stage on the part of the muzzle derived from the medial nasal prominence. Thus the so-called mystacial vibrissae should be subdivided into three (or 4, including the rhinal) groups on an embryological basis. They are the lateral nasal, the maxillary and the labial. A supernumerary sinus hair and a corresponding barrel was observed between D and C rows uni-or bilaterally in one third of individuals of BALB/c, nude and hairless mice. It is suggested that supernumerary hairs tend to occur between the groups of hairs as defined above. In nude and hairless mice small barrels representing labial hairs are diminished in number. The number of hair follicles, however, is normal.