Fetal developmental change in topographical relationship between the human lateral pterygoid muscle and buccal nerve.

In adults, the lateral pterygoid muscle (LPM) is usually divided into the upper and lower heads, between which the buccal nerve passes. Using sagittal or horizontal sections of 14 fetuses and seven embryos (five specimens at approximately 20-25 weeks; five at 14-16 weeks; four at 8 weeks; seven at 6-7 weeks), we examined the topographical relationship between the LPM and the buccal nerve. In large fetuses later than 15 weeks, the upper head of the LPM was clearly discriminated from the lower head. However, the upper head was much smaller than the lower head in the smaller fetuses. Thus, in the latter, the upper head was better described as an 'anterior slip' extending from the lower head or the major muscle mass to the anterior side of the buccal nerve. The postero-anterior nerve course seemed to be determined by a branch to the temporalis muscle (i.e. the anterior deep temporal nerve). At 8 weeks, the buccal nerve passed through the roof of the small, fan-like LPM. At 6-7 weeks, the LPM anlage was embedded between the temporobuccal nerve trunk and the inferior alveolar nerve. Therefore, parts of the LPM were likely to 'leak' out of slits between the origins of the mandibular nerve branches at 7-8 weeks, and seemed to grow in size during weeks 14-20 and extend anterosuperiorly along the infratemporal surface of the prominently developing greater wing of the sphenoid bone. Consequently, the topographical relationship between the LPM and the buccal nerve appeared to 'change' during fetal development due to delayed development of the upper head.

Skeletal units of the human embryonic mandible.

The development of the mandible was traced on serial sections of 20 human embryos aged 5-8 weeks (developmental stages 13-23). Special consideration was given to the differentiation of skeletal units proposed by Sperber. The first skeletal units, namely the mandibular body, the alveolar unit and the condylar unit, may be distinguished in the 7(th) week. The primordia of all units are identified by the end of the embryonic period (8 weeks).

Early development and innervation of taste bud-bearing papillae on the rat tongue.

Early development of fungiform papillae on the fetal rat tongue was examined: (1) to determine whether morphogenesis of the taste bud-bearing fungiform papillae is induced by nerve and (2) to study the growth pattern of the two sensory nerves that innervate the papilla. The papillae first appear on the 15th day of gestation (E15; E1 is the day when the dam is sperm positive) in rows parallel to the midline sulcus. There appears to be a medial-lateral and an anterior-posterior gradient in the sequence of papilla differentiation. The epithelium of the early papilla resembles a multilayered placode topped by a flattened surface periderm. Close examination of the peridermal cells at the apex of the papillae reveals that the cells have fewer surface microvilli and their cytoplasm is more electron opaque than that of similar cells in interpapillary regions. The basal cells in the placode-like epithelium differ from those in interpapillary regions in that they are postmitotic and have more mitochondria. At later stages, the papilla acquires a mesenchymal core and nerves grow into the core. Results from organ culture experiments of tongue fragments taken from E14 fetuses indicate that morphogenesis of fungiform papillae is initiated in the absence of sensory nerve influence, but the nerve exerts a trophic effect on their maintenance. The two sensory nerves of the tongue, the chorda tympani and the lingual branch of the trigeminal nerve, enter the tongue mesenchyme at E14 and grow toward the epithelium. By E15 the chorda tympani branches have reached the developing fungiform papillae, by E16 many have entered the papilla, and by E17 they have penetrated the epithelium at the papilla apex. Their fibers are associated exclusively with the cells at the papilla apex, where the taste bud will develop. The trigeminal nerve ramifies beneath the surface of the entire epithelium by E15. Later, it, too, sends branches into fungiform papillae; these ascend along the trunk of the chorda tympani and at E17 terminate in the connective tissue core around the chorda tympani field. The results are compatible with the notion that the tongue epithelium exerts a general tropic effect on growing axons of both sensory nerves, and the epithelial cells of the fungiform papilla apex exert a similar effect to which only the chorda tympani axons are responsive.

The human mandibular canal arises from three separate canals innervating different tooth groups.

The purpose of this study was to describe the prenatal formation of the human mandibular canal. Since bony canals develop in prenatal life around the nerve paths, it was assumed that the canal pattern could reflect the pattern of innervation of the dentition. Mapping of this early canal pattern does not appear to have been undertaken before. The material consisted of anthropological mandibles from the National Institute of Anthropology and History, Mexico City. A total of 302 human hemimandibles from the latter half of the prenatal period was investigated. The length, measured from the mental symphysis to the mandibular condyle, ranged from 28 to 60 mm. The dento-alveolar maturity was classified in two stages according to the appearance of alveolar sockets of deciduous and first permanent molars. The mandibles were radiographed with guttapercha points inserted into the canal openings (foramina) on the lingual surfaces of the mandibular rami. The study showed that the canal to the incisors appeared first, followed by the canal to the primary molars, and last by the one or more canals to the first permanent molars. In the most mature group, three different canals always occurred in each hemimandible. The canals were directed from the lingual surface of the mandibular ramus toward the different tooth groups. The inferior alveolar nerve presumably occurs in the mandible as three individual nerve paths originating at different stages of development. It is suggested that rapid prenatal growth and remodeling in the ramus region result in a gradual coalescence of the canal entrances that is obvious at birth. It is hypothesized that the pattern of tooth agenesis within the three groups of teeth is related to the three separate paths of innervation of the dentition.

Myogenic determination and differentiation of the mouse palatal muscle in relation to the developing mandibular nerve.

The vertebrate palatal muscles are derived from the cranial paraxial mesoderm and start myogenesis by the expression of myogenic regulatory factors (MRFs). Predetermined myogenic cells migrate from the cranial paraxial mesoderm into the branchial arches, followed by myogenic differentiation. The objective of this study was to elucidate whether the determination, migration, and differentiation of myogenic cells during the myogenesis of the palatal muscles, particularly the tensor veli palatini (TVP), are related to the extending mandibular nerve in mouse embryos. By immunohistochemical staining at embryonic day (E) 9.5, MyoD1 and myogenin have been expressed in the mandibular arch, into which the mandibular nerve had not yet extended. At E11.5, these myogenic cells encircled the extending mandibular nerve and were distributed from the distal and lateral to the trigeminal ganglion and into the mandibular arch to form the muscle plate, a girdle-like structure. By E12.5, these myogenic cells lost their girdle-like pattern, vacated the trunk area of the mandibular nerve, and were separated into several incompletely divided masses encircling the collateral branches of the mandibular nerve. The TVP started differentiation at E13.5 with the appearance of myofilaments and acetylcholinesterase (AchE), whereas the other palatal muscles began differentiation at E14.5. We defined the differentiation process of mouse palatal muscles into five stages based on the present findings. These results suggest that the determination and initial migration of the palatal myogenic cells into the mandibular arch occur before the mandibular nerve extends out of the trigeminal ganglion, whereas the myogenic cells migrating into the final sites of differentiation intimately relate to the extending nerve.

Reconstructing the pathway of the tensor veli palatini motor nerve during early mouse development.

The motor axons innervating the tensor veli palatini (TVP) navigate a long distance from the trigeminal motor nucleus to their target. The pathway and time course of the TVP motor nerve during this navigation process remain poorly understood. The aim of this study was to elucidate the peripheral development of the TVP motor nerve, and to confirm when the morphological relationship is established between the nerve and target muscle progenitors. Using immunohistochemistry, carbocyanine fluorescent labeling, and computerized three-dimensional image-reconstruction methods, we demonstrated the development of the TVP motor nerve in mouse embryos. Further, the morphological relationship between the extending mandibular nerve and myogenic cells stained for MyoD1 was examined. The peripheral pathfinding of the TVP motor nerve was divided into three continuous stages: (1) the earliest trigeminal motor axons leave the metencephalon and enter the primordium of the trigeminal ganglion at E9.5, when MyoD1-positive cells can already be detected in the mesenchymal core of the mandibular arch; (2) converging with the sensory root, the trigeminal motor root excites the trigeminal ganglion and begins to approach the mandibular muscle precursors at E10.5; (3) collateral branching occurs at E12.5. By E13.5, a nerve branch splits from the mandibular nerve to innervate the TVP, which appears as an individual muscle mass. These results suggest that the early process of mandibular motor nerve extension is correlated with the trigeminal ganglion cells, whereas when growing out of the ganglion, the mandibular nerve has a close relationship with target myogenic cells throughout the later process of pathway finding.

Topography of the inferior alveolar nerve in human embryos and fetuses: an histomorphological study

The aim of this study is to establish the position of the inferior alveolar nerve in relation to the Meckel's cartilage, the anlage of the mandibular body and primordia of the teeth, and also to trace the change in nerve trunk structure in the human prenatal ontogenesis. serial sections (20µm) from thirty-two 6-12 weeks-old entire human embryos and serial sections (10µm) of six mandibles of 13-20 weeks-old human fetuses without developmental abnormalities were studied. histological sections were impregnated with silver nitrate according to Bilshovsky-Buke and stained with hematoxylin and eosin. during embryonic development, the number of branches of the inferior alveolar nerve increases and its fascicular structure changes. in conclusion, the architecture of intraosseous canals in the body of the mandible, as well as the location of the foramina, is predetermined by the course and pattern of the vessel/nerve branching in the mandibular arch, even before the formation of bony trabeculae. particularly, the formation of the incisive canal of the mandible can be explained by the presence of the incisive nerve as the extension of the inferior alveolar nerve. It has also been established that Meckel's cartilage does not participate in mandibular canal morphogenesis.

Development of the juxta-oral organ in rat embryo.

The aim of this work is to clarify the development and morphology of the juxta-oral organ (JOO) in rat embryos from Day (E)14 to 19. Furthermore, in the region of the JOO, an analysis was made of the expression of the monoclonal antibody HNK-1, which recognizes cranial neural-crest cells. In this study, we report that JOO develops from an epithelial condensation at the end of the transverse groove of the primitive mouth at E14. During E15, it invaginates and is disconnected from the oral epithelium. At E16, the JOO forms an solid epithelial cord with three parts (anterior, middle, and posterior) and is related to the masseter, temporal, medial pterygoid, and tensor veli palatini muscles. During E17-19, no significant changes were detected in their position. Both the mesenchyme caudal to the anlage of the JOO at E14, as well as the mesenchyme that surrounds the bud of the JOO at E15, expressed positivity for HNK-1. Our results suggest that the mesenchyme surrounding the JOO at E15 could emit some inductive signal for the JOO to reach its position at E16. This work shows for the first time that the cranial neural-crest-derived mesenchyme participates in the development of the JOO.

Embryonic development of the mandibular canal.

On the basis of examination of 50 fetal mandibles, development of the mandibular canal is described. The development of the foramen mandibulae, foramen mentale, the lingula, the alveolar process, and the morphological changes in the mandible due to the effect of the development of the mandibular canal are discussed. The anatomical conditions examined may also have clinical implications.

Bone remodeling during prenatal morphogenesis of the human mental foramen.

From a morphogenetic point of view, the mental foramen of the mandible is a highly suitable model to study the interactions of different tissues such as nerves, vessels, mesenchymal cells, cartilage, and bone. In previous work, we provided a three-dimensional description of the mental foramen at different developmental stages, and now we complement those studies with a three-dimensional visualization of different bone remodeling activities around the mental foramen. Histological serial sections of human embryos and fetuses, ranging in size from 25 to 117 mm crown-rump-length (CRL), were used to characterize the bone remodeling activity (apposition, inactivity, and resorption). We quantified and reconstructed this activity in three dimensions, and included information on the spatial relationship of the nerves, vessels, and dental primordia. In general, the mandible showed strong apposition at its outer surfaces. The brim of the mental foramen, however, displayed changing remodeling activity at different stages. In the depth of the bony gutter, which provides space for the nerve and the blood vessels, we found bone resorption beneath the inferior alveolar vein. Bone was also resorbed in proximity to the dental primordia. In future studies, we will relate gene expression data to these morphological findings in order to identify molecular mechanisms that regulate this complex system.

Peripheral development of avian trigeminal nerves.

Development of the trigeminal nerve branches was studied in stage -17 to -27 chick embryos stained with an antibody to neurofilament protein. The following findings were obtained. 1) Ectopic ganglia transiently appeared in the ectoderm of the supraorbital region and were considered as remnant ophthalmic-placode-derived ganglia. 2) Most of the cutaneous sensory branches of the maxillomandibular nerve arose from a loosely arborized mass of neurites, provisionally termed the maxillomandibular reticulum, in which the fibers intermingled in a seemingly random fashion. 3) The growth of the trigeminal branches was mainly correlated with the development of the facial processes; however, irregular communications between different groups of branches were observed, suggesting that topographical organization of the peripheral branches is not rigid in early stages. 4) From the ophthalmic nerve around stage 23, transient dorsal rami developed and were distributed in the mesenchymal space, the cavum epiptericum, and passed near the ectoderm. Their homology with the rr. tentorii in human anatomy is suggested.

Study of pterygospinosus muscle in human fetuses.

The arrangement of the pterygospinosus muscle was analyzed in 5 human fetuses. The pterygospinosus muscle extends from the posterior border of the lateral lamina of the pterygoid process to Meckel's cartilage. Such an arrangement would permit its action on the joint formed by Meckel's cartilage and the incus of the middle ear. The pterygospinosus muscle is a remnant of the masticatory muscle group. The relationships of the pterygospinosus muscle with the mandibular nerve and its branches and the maxillary artery and its branches were analyzed.

Trigeminal ganglion axons are repelled by their presumptive targets.

Previous work suggested that in mouse, presumptive targets of the trigeminal ganglion, rather than intermediate structures, attract pioneer axons from the time their growth cones exit the ganglion (Lumsden and Davies, 1986). In rat we find that some presumptive targets repel trigeminal axons. The repellant activity is concentrated in the anterior and ventral epithelium of the mandibular arch at embryonic day 12 (E12) and was also present in the maxillary arch. The activity is blocked by anti-neuropilin-1. E13 mandible explants repel trigeminal axons during the first day of outgrowth in vitro, but thereafter permit or attract trigeminal ganglion axon outgrowth. By E14, lingual nerve afferents first enter the tongue in vivo, and the repellant influence becomes restricted to the midline. The progressive restriction of the repellant influence may contribute to the in vivo progression of nerve development: the earliest afferents turn anteriorly lateral to the tongue, but subsequently arriving afferents advance into the tongue and then turn away from the midline. Thus, the repellant may influence the order of nerve branch development and the timing of innervation of epithelial and subepithelial targets. Heterochronic studies revealed that the loss of repellant influence from presumptive lateral tongue surface results from downregulation of the repellant activity, not of responsiveness to the repellant. Because presumptive targets repel trigeminal axons during the initial stages of advance from the trigeminal ganglion and do not have a net attractive influence until after afferents have arrived near the target, intermediate structures must guide these axons initially.

The development of the peripheral trigeminal innervation in Xenopus embryos.

The development of the ophthalmic, maxillary and mandibular nerves has been followed in Xenopus laevis embryos from the first emergence of growth cones from the trigeminal ganglia until the establishment of functional innervation of the skin or cement gland. The course of each main nerve is highly predictable and follows pre-existing openings between blocks of other tissues. The development of the mandibulary nerve was observed most easily. Like that of the other trigeminal nerves it falls into three stages: (1) A pioneer neurite emerges and a nerve forms as other, later neurites fasciculate with this. (2) On reaching the inside surface of the cement gland the neurites separate and penetrate holes in the basal lamina. (3) The neurites grow between the cells they will innervate and form free nerve endings. The scanning EM observations have been confirmed by electrical recordings from trigeminal neurones. The role of pioneer fibres and substrate guidance are discussed.

Formation and early prenatal location of the human mental foramen.

The formation and early prenatal location of the human mental foramen was investigated on 43 human fetuses. Histochemical methods supplemented by macroscopic visualization were used. Similar studies on the mental foramen were not available in the literature. The study demonstrated constancy in the developmental sequence of the bony structures in the region of the mental foramen. The formation of the mental foramen was described and related to general developmental parameters such as CRL and CNO values (skeletal maturity indexes of the hand and foot). The study indicated that the very early position of the mental foramen was in the region of the interstitial bone between the primary canine and the primary first molar. A positional change in the dorsal direction was described during the first half of the prenatal period.

Correlated appearance of ossification and nerve tissue in human fetal jaws.

The factors initiating the onset of desmal jaw formation are not known. The purpose of the present report was to examine the correlation between the appearance of ossification and nerve tissue in human fetal jaws. This was done through elaboration of similarities in occurrence of tissue types at four different sites of initial bone formation in the jaws. Radiological and histochemical methods applied to the jaws of 26 human embryos/fetuses revealed that nerve tissue appeared in the jaws before bone tissue. Early bone formation occurred in close relation to the mandibular nerve, the maxillary nerve, the palatine nerve, and the naso-palatine nerve. It is suggested that the foramina (mental foramen, infraorbital foramen, palatal foramen, and incisive foramen) are the areas of incipient bone formation, and that the sequence in bone formation corresponds to the sequence in the development of nerve fibers from the trigeminal ganglion.

Prenatal morphogenesis of the human mental foramen.

The mental foramen, at first glance, merely looks like a hole where the mental nerve and the vascular bundle runs through. From a morphogenetic point of view, however, the mental foramen is a suitable model to study the development of a structure where different components are involved. To understand this developmental process, a three-dimensional description at different developmental stages first has to be given. From histological serial sections of human embryos and fetuses, ranging in size from 19 to 117 mm crown rump length (CRL), three-dimensional reconstructions of the foraminar regions were made. Outline and form of the developing foramen, size, course of the mental nerve and the adjacent blood vessels could be shown in detail. In this way, the formation of these structures became concrete in three dimensions. In the future, to understand the mechanisms regulating this complex system, where a nerve and blood vessels became successively surrounded by bone, molecular biological data have to be correlated with morphological findings.

Variation in the origin of the inferior alveolar nerve.

The inferior alveolar nerve and maxillary artery were studied in 40 human heads through infratemporal dissection; in one specimen, a unusual variation in the origin of the inferior alveolar nerve and its relationship with the surrounding structures was observed. The inferior alveolar nerve originated from the mandibular nerve by two roots and the second part of the maxillary artery was incorporated between them. An embryologic origin of this variation and its clinical implications is discussed. Because the maxillary artery ran between the two roots of the inferior alveolar nerve, and the nerve was fixed between the foramen ovale and mandibular foramen, tension and compression of the nerve from arterial pulsation could cause mandibular neuralgia.