Perlecan, a heparan sulfate proteoglycan, is one of the major basement membrane macromolecules and plays an important role in cellular growth, differentiation, adhesion, and motility by its interaction with growth factors and cytokines. Recently, perlecan has been localized within the epithelial space in various pathophysiological conditions. As the intraepithelial accumulation of perlecan results in widening of the intercellular space, the most characteristic example of such phenomena is the stellate reticulum of the enamel organ of tooth germs, whose structure and function have been largely unknown. Stellate reticulum-like structures are also found in pathological conditions such as ameloblastoma or oral epithelial dysplasia. The biosynthesis of perlecan has been demonstrated in those epithelial cells, and such peculiar stellate reticulum appearances are shown to be due to intercellular deposits of over-expressed perlecan. However, when perlecan is transgened into mouse epithelial tissue using the keratin 5 promoter, the tooth cannot be formed normally. Thus, a constant over-expression of perlecan interferes with normal development. The time schedule of the intraepithelial expression of perlecan seems to be controlled critically in the process of odontogenesis. In this review article, we address the current views on the structure and function of perlecan acting in the intraepithelial stromal space, with special attention to its role in tooth morphogenesis.

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Neurological studies in patients with stroke or epilepsy have suggested that the human primary gustatory cortex is located in the insula and frontal operculum. Although electrophysiological studies in non-human primates have supported the above idea, these conventional approaches were inapplicable to systematically examine the human gustatory cortex. Recent non-invasive brain imaging techniques including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have enabled us to explore the precise locations of gustation-related regions in the human brain. These non-invasive imaging studies have revealed the mechanism of not only “bottom-up” information processing, from the peripheral gustatory organs, taste buds, to the gustatory cortices, but also “top-down” processing in the gustatory system. Our group investigated the organization of neural systems for gustatory perception and gustatory imagery using fMRI. We found that gustatory imagery tasks activate the insula, showing predominant activation in the left hemisphere. Furthermore, gustatory imagery tasks activated the orbitofrontal, precentral, and middle/superior frontal gyri. On the other hand, gustatory imagery contrasted with visual imagery activated only the insula, orbitofrontal and precentral gyri. These results suggest the possibility that the source of “top-down” signals may be in the middle and superior frontal gyri, and that these signals may affect on neural activities in the insula, orbitofrontal, and precentral gyri.

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Signs of disease thought to indicate a fibro-osseous disorder were found in a mandible of human skeletal remains from the Kofun period in Japan. The skeletal remains were found in an excavation in Yamato City, Kanagawa Prefecture. Fibro-osseous disorder encompasses several diseases. The case in this report was a male in his 30s who had bilateral lesions in the mandibular molar regions with bony structures having well-defined margins. The left molar region showed considerable destructive resorption towards the mandibular base, and periosteomyelitis was thought to have accompanied it. The differential diagnosis of fibro-osseous disorder is difficult. However, the lesions were speculated to be osseous dysplasia based on radio-opacities on radiographs and CT scans and the lack of metastasis in the bones of the trunk, in addition to other findings. In other words, the lesions were comprehensively determined to have been benign and not malignant. No previous report has been made on the discovery of osseous dysplasia in excavated ancient human skeletal remains. Therefore, this case is considered to be very important.

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Glial cell line-derived neurotrophic factor (GDNF) acts to promote the development, survival, and maintenance of central and peripheral neurons. Using RT-PCR analysis and immunohistochemical observations by both light and electron microscopy, we examined whether the myoepithelial cells in the major and minor salivary glands of normal mice expressed GDNF. RT-PCR analysis revealed the existence of mRNAs of GDNF and its receptor, GFRα1, in the submandibular glands. The immunoelectron microscopic observations showed that the GDNF-immunoreactive cells were located between the acinar secretory cells and the basement membrane, with their slender cytoplasmic processes containing bundles of filaments extending along the basement membrane, thus revealing them to be myoepithelial cells. Double immunostaining with anti-GDNF and anti-actin by confocal laser scanning microscopy in each gland revealed that most of these GDNF-immunoreactive cells were also actin-immunopositive. Numerous PGP9.5-immunoreactive nerve fibers were distributed in the serous glands of the parotid, submandibular, and Ebner glands (glands of von Ebner), which had less developed myoepithelial cells; although Ebner glands had relatively more developing myoepithelial cells than the other two glands. On the other hand, the mucous glands of the sublingual gland and tongue mucous glands had sparse nerve fibers but highly developed myoepithelial cells. Thus, the degree of myoepithelial cell development was almost in inverse proportion to the degree of innervation.

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Tongue pressure against the anterior and posterior portions of the hard palate as well as the electromyographic activity of suprahyoid muscle during swallowing test foods with three different consistencies (thinned, medium, and thickened paste) and liquid were recorded. Significant differences and wide variations were noted in the peak amplitude and area of posterior tongue pressure, which was larger for thickened paste compared to liquid, thinned, and medium pastes. Regarding the anterior tongue pressure, the duration was significantly longer during swallowing thickened paste compared to liquid and thinned paste, while there were no differences in the peak amplitude and area. The results suggest that a basic pattern of tongue pressure is maintained during swallowing but is modulated by sensory feedback in a different manner between the anterior and posterior portions of the tongue to complete propulsion of the bolus in the oral cavity.

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The present study aimed to investigate the pathways and fates of medial edge epithelial (MEE) cells in organ culture of the mouse palatal shelve in combination with vital-dye labelings and in situ confocal observation of labeled MEE cells. Embryos at E13.5-13.7 were used to collect palatal shelves for organ culture. Epithelia of the palatal shelves were labeled with two fluorochromes, CCFSE and DiI. The organ culture was validated histomorphologically to assimilate in vivo palatogenesis at least with respect to sequential events at the midline, i.e., the formation and discontinuity of the epithelial seam and the mesenchymal confluence. Immunohistochemistry showed that extensive cell death was evoked at the midline seam and triangles over the entire fusion processes. Alexa-tagged ssDNA immunostaining showed that, by 6 h after the MEE cells were placed in contact, the first sign of cell death was observed within the intact epithelial seam, distributing along the whole length of the midline seam as well as the triangle. A majority of the labeled MEE cells exhibited motility and followed pathways toward the oral and nasal ends, where the triangular morphology was generated. A relatively small number of MEE cells crossed over the basal lamina and executed phenotypic changes in the mesenchyme. The combined localization of the fluorescence and cytokeratin markers confirmed a loss of epithelial phenotype in fractions of the MEE cells after their migration into the mesenchyme. Their histological appearance indicated that they remained viable after leaving the epithelial population. These results support the theory that multiple cellular events, namely apoptosis, migration, and epithelial-mesenchymal transformation (EMT), most likely contribute to palatal shelf fusion and that apoptosis may be a major contributor for the removal of MEE cells and activation of adjacent MEE cells.

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