Neuroepithelial Structures Research Articles

Neuroepithelial Structures of the Oral Soft Tissues Including the Juxtaoral Organ of Chievitz: A Literature Review and Audit of Diagnosed Cases

The juxtaoral organ of Chievitz (JOOC) is a part of microanatomy composed of bland epithelial islands closely associated with small nerves and usually described within the soft tissue on the lingual aspect of the posterior mandible. Similar structures are documented in the posterior tongue. There is a risk of misinterpretation as carcinoma showing perineural invasion. An audit was undertaken of diagnosed cases of the JOOC and similar neuroepithelial structures identified within the oral soft tissues of surgical specimens. Nineteen cases were identified. Epithelial islands ranged < 0.5–4 mm in maximum dimension and lay in close association with small nerves. Epithelial cells showed a squamoid appearance but were without keratinisation. There was no atypia and mitotic figures were not seen. In 53% of cases the epithelial cells showed cytoplasmic clearing, in 26% of cases there was brown pigment and in 11% of cases there were calcifications. In 53% of cases, these neuroepithelial structures lay within the soft tissue lingual to the mandible in the retromolar area, 26% of the structures were placed buccal to the mandible, 11% of the structures lay adjacent to the maxillary tuberosity and 11% of the structures were within the posterior tongue.

PDTM-35. MODELLING MEDULLOBLASTOMA WITH MOUSE MODELS AND HUMAN CEREBELLAR ORGANOIDS

Abstract Malignant medulloblastoma (MB) is the most common brain tumor affecting children and it remains responsible for a high percentage of morbidity and mortality among cancer patients. During the past few years, studies on human MB and mouse models have uncovered the existence of four major MB groups, with specific pathological and molecular features: WNT, SHH, Group 3 and Group 4. Of the four groups, patients with Group 3 MB have the worst outcome with nearly 50% of the tumors metastatic at the time of diagnosis. Therefore, developing “humanized “ mouse model of Group3 Medulloblastoma would be of paramount importance for the identification and testing of new drugs for pediatric patients, tailored on the genetic condition of the patient itself. We performed an in-vivo screen to identify new cancer-inducing genes starting from the published genome-wide analyses of MB patients. This screen led to the identification of novel driver gene combinations required for tumorigenesis. To study Medulloblastoma in human cells, we generated human cerebellar organoids. Organoids are cellular structures that resemble whole organs and can be generated from pluripotent stem cells or isolated organ progenitors. We were able to induce cerebellar progenitors to self-form neuro-epithelial structures that mimic early human cerebellar plate, composed by cerebellar progenitors, cerebellar neurons (interneurons, Purkinje cells, and granule neurons) and glial cells. Notably, we have generated human putative iPSC-derived cancer organoids with gene combinations mimicking human Group3 MB. Indeed, organoids that mimic cancer can be used as an alternative system for drug testing that better recapitulate effects in human patients as compared to other in-vitro and in-vivo systems.

Hearing loss in acute respiratory infections

Upper airway inflammatory diseases account for about 90% of all infectious diseases and are the most common causes of patients’ visits to the otorhinolaryngologists, pediatricians and general practitioners. Acute otitis media and rhinosinusitis are considered the most common complications of acute respiratory infections. Auditory disorders often occur during respiratory infections, which may be directly caused by Eustachian tube dysfunction, acute otitis media and acute sensorineural hearing loss. Sensorineural hearing loss (SNHL) is a type of diminished hearing (up to loss), which affects any of the parts of the soundperceiving apparatus of the auditory analyser, ranging from the neuroepithelial structures of the inner ear to the cortical representation in the temporal lobe of the cerebral cortex. It is extremely important to timely detect sensorineural hearing loss and immediately start therapeutic measures, especially in children, since de-socialization occurs much faster in this age group.

Self-organizing cortex generated from human iPSCs with combination of FGF2 and ambient oxygen

Human brain development has generally been studied through the analysis of postmortem tissues because of limited access to fetal brain tissues. This approach, however, only provides information from the perspective of long-term development. To investigate the pathophysiology of neurodevelopmental disorders, it is necessary to understand the detailed mechanisms of human brain development. Recent advances in pluripotent stem cell (PSC) technologies enable us to establish in vitro brain models from human induced PSCs (hiPSCs), which can be used to examine the pathophysiological mechanisms of neurodevelopmental disorders. We previously demonstrated that self-organized cerebral tissues can be generated from human PSCs in a three-dimensional (3D) culture system. Here, we describe the cerebral tissues differentiated from hiPSCs in a further-optimized 3D culture. We found that treatment with FGF2 is helpful to form iPSC aggregates with efficiency. Neuroepithelial structures spontaneously formed with apico-basal polarity in the aggregates expressing forebrain marker FOXG1. The neuroepithelium self-forms a multilayered structure including progenitor zones (ventricular and subventricular zones) and neuronal zone (cortical plate). Furthermore, with the same level of oxygen (O2) as in ambient air (20% O2), we found that self-formation of cortical structures lasted for 70 days in culture. Thus, our optimized 3D culture for the generation of cortical structure from hiPSCs is a simple yet effective method.

The origins of the circumventricular organs.

The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They mediate the communication between the brain and the periphery by performing sensory and secretory roles, facilitated by increased vascularisation and the absence of a blood-brain barrier. Surprisingly little is known about the origins of the CVOs (both developmental and evolutionary), but their functional and organisational similarities raise the question of the extent of their relationship. Here, I review our current knowledge of the embryonic development of the seven major CVOs (area postrema, median eminence, neurohypophysis, organum vasculosum of the lamina terminalis, pineal organ, subcommissural organ, subfornical organ) in embryos of different vertebrate species. Although there are conspicuous similarities between subsets of CVOs, no unifying feature characteristic of their development has been identified. Cross-species comparisons suggest that CVOs also display a high degree of evolutionary flexibility. Thus, the term 'CVO' is merely a functional definition, and features shared by multiple CVOs may be the result of homoplasy rather than ontogenetic or phylogenetic relationships.

Neuroepithelial structures associated with the subepithelial nerve plexus of taste buds: a fortuitous finding resembling the juxtaoral organ of Chievitz

Numerous embryologic epithelial remnants are described in the oral region, when intimately associated with peripheral nerves, may pose a diagnostic pitfall for pathologists. The literature contains cases in which the juxtaoral organ of Chievitz (JOC) was identified in specimens removed because of a malignancy and the correct recognition of this structure potentially avoids unnecessary treatment. To our knowledge, this is the description of neuroepithelial structures similar to the JOC were found in the posterior tongue in close association with the subepithelial nerve plexus of taste buds. Four cases are reported. The nerve fibers of the subepithelial nerve plexus showed strong positivity for S-100, CD56, and synaptophysin, and were intimately associated with epithelial islands. CD56 showed positivity around the periphery of the epithelial islands. Proper recognition of these anatomic structures is crucial to prevent misdiagnosis of squamous cell carcinoma with perineural invasion.

Neuroepithelial Structures Associated With the Subepithelial Nerve Plexus of Taste Buds: A Fortuitous Finding Resembling the Juxtaoral Organ of Chievitz Case Report and Review of the Literature

Numerous embryologic epithelial remnants have been described in the oral region, and when they are intimately associated with peripheral nerves, they may pose a diagnostic pitfall for pathologists. The literature contains well-documented cases in which the juxtaoral organ of Chievitz (JOC) was identified in a surgical specimen removed because of an oral malignancy and correct recognition of this anatomic structure potentially avoided unnecessary treatment. To the best of our knowledge, this is the first report of such a case in which a neuroepithelial structure similar to, if not morphologically identical to, that of the JOC was found in the posterior lateral border of the tongue in close association with the subepithelial nerve plexus of taste buds.

Left-Right Locomotor Circuitry Depends on RhoA-Driven Organization of the Neuroepithelium in the Developing Spinal Cord

RhoA is a key regulator of cytoskeletal dynamics with a variety of effects on cellular processes. Loss of RhoA in neural progenitor cells disrupts adherens junctions and causes disorganization of the neuroepithelium in the developing nervous system. However, it remains essentially unknown how the loss of RhoA physiologically affects neural circuit formation. Here we show that proper neuroepithelial organization maintained by RhoA GTPase in both the ventral and dorsal spinal cord is critical for left-right locomotor behavior. We examined the roles of RhoA in the ventral and dorsal spinal cord by deleting the gene in neural progenitors using Olig2-Cre and Wnt1-Cre mice, respectively. RhoA-deleted neural progenitors in both mutants exhibit defects in the formation of apical adherens junctions and disorganization of the neuroepithelium. Consequently, the ventricular zone and lumen of the dysplastic region are lost, causing the left and right sides of the gray matter to be directly connected. Furthermore, the dysplastic region lacks ephrinB3 expression at the midline that is required for preventing EphA4-expressing corticospinal neurons and spinal interneurons from crossing the midline. As a result, aberrant neuronal projections are observed in that region. Finally, both RhoA mutants develop a rabbit-like hopping gait. These results demonstrate that RhoA functions to maintain neuroepithelial structures in the developing spinal cord and that proper organization of the neuroepithelium is required for appropriate left-right motor behavior.

Conditions for Tumor-free and Dopamine Neuron–enriched Grafts After Transplanting Human ES Cell–derived Neural Precursor Cells

We have previously demonstrated derivation of neural precursor (NP) cells of a midbrain-type from human embryonic stem (hES) cells to yield an enriched population of dopamine (DA) neurons. These hES-derived NPs can be expanded in vitro through multiple passages without altering their DA neurogenic potential. Here, we studied two aspects of these hES-NP cells that are critical issues in cell therapeutic approaches for Parkinson's disease (PD): cell survival and tumorigenic potential. Neuroepithelial rosettes, a potentially tumorigenic structure, disappeared during hES-NP cell expansion in vitro. Although a minor population of cells positive for Oct3/4, a marker specific for undifferentiated hES cells, persisted in culture during hES-NP cell expansion, they could be completely eliminated by subculturing hES-NPs under differentiation-inducing conditions. Consistently, no tumors/teratomas are formed in rats grafted with multipassaged hES-NPs. However, extensively expanded hES-NP cells easily underwent cell death during differentiation in vitro and after transplantation in vivo. Transgenic expression of Bcl-XL and sonic hedgehog (SHH) completely overcame the cell survival problems without increasing tumor formation. These findings indicate that hES-NP cell expansion in conjunction with Bcl-XL+SHH transgene expression may provide a renewable and safe source of DA neurons for transplantation in PD.

P73 isoforms expression in the cerebrospinal fluid and circumventricular organs of BPH mice and SHR rats

Background It has been reported that the blood pressure high (BPH) mouse shows an increase in blood pressure and alterations in the brain catecholaminergic system as well as normal ventricular size. However, spontaneously hypertensive rats (SHR) show ventricular dilation, changes in CSF proteins and variations in the brain angiotensin-vasopressin system. The subcommissural organ (SCO), the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and the area postrema (AP) are circumventricular organs (CVO) located in the third and fourth ventricle which are rich in neuropeptides such as angiotensin II and catecholamines Variations in the SCO have been reported in hydrocephalus and hypertension. The SFO has connections with the brain regions involved in the central regulation of blood pressure and cardiovascular function. The p73 isoforms function as essential pro-survival molecules in both the CNS and PNS and are important not just during the period of developmental death but also for the maintenance of at least some populations of adult neurons. In the absence of p73, ventricular enlargement occurs as neurons degenerate and tissue mass decreases, a phenomenon also observed in the degenerating human brain. The purpose of the present work is to study the TAp73 and ΔNp73 expression in neuroepithelial structures such us: the CVO and their variations in ventricular dilatation and arterial hypertension.

Developmental dynamics and maturation of transplanted human embryonic stem cell-derived neural precursors in the adult rodent CNS

Human embryonic stem cells (HESC) are an unlimited source of cells for stem cell therapies. We investigated the dynamics of integration of HESC-derived neural precursors (NPs) into host neural circuitry. Methods: NP cultures were derived from the NIH-approved HESC line BG01 with noggin in B27/N2-supplemented medium. These NPs were grafted into the forebrain and ventral brain stem of immunodeficient rats (NIH-RNU). Brain tissues were prepared at 6, 15 and 26 weeks post-grafting. Results: The HESC-NPs showed a site-dependent fate, i.e. a greater mitotic activity and ongoing neuroepithelial structure formation in the brain stem and a lower mitotic activity and eventual resolution and dedifferentiation of early neuroepithelial structures in the forebrain. The later almost disappeared at 15 weeks post-grafting. By 15 weeks, a large percentage (57.8–80.8%) had differentiated into early (TUJ-1[+]) neurons that extended axons along pre-established CNS pathways (cortico-striatal, internal capsule, external capsule) and formed dense synaptic fields, especially in the graft area in the form of local innervation and in the host subventricular zone (SVZ). An especially strong affinity for SVZ and the pia mater was noted. Some migration was seen along white matter tracts; in the case of ventral brain stem injections, migration of nestin/NCAM (+) precursors could be followed several segments down the cervical cord. The extensive ability of HESC-NPs to differentiate into neurons, migrate and possibly establish synaptic contacts with other graft and host cells demonstrates their potential to repair neural circuits damaged by either trauma or neurodegeneration. The successful outcomes of human NP xenografts in rats demonstrate the value of human-to-rodent experimental approaches in the preclinical evaluation of human ES cells. In addition, HESNPs may prove to be valuable instruments for studying novel inductive signals that influence not only graft differentiation and integration, but also host repair mechanisms, including neurogenesis and synaptic plasticity after trauma.

Formation of Neuroepithelial Structures in Culture of Neural Stem Cells from Human Brain

Dissociated fetal brain cells in a floating culture form clusters and then neurospheres, some of which contain structures shaped as cell "rosettes". The cells in these "rosettes" are arranged radially around the central cavity, in which their apical processes form desmosome-like contacts. Mitotic division of cells in the "rosettes" is associated with migration of the nuclei, similarly to division of neuroepithelial cells in the neural tube during normal embryogenesis. These cells express nestin, a marker of neural stem cells. The cells in "rosettes" found after transplantation have similar characteristics.

β‐catenin–mediated cell‐adhesion is vital for embryonic forebrain development

Forming a complex structure such as the mammalian brain requires a complex interplay between cells and different signalling cascades during embryonic development. beta-catenin plays pivotal roles in these processes by mediating cadherin-based cell adhesion and Wnt signalling. We show for the first time that beta-catenin functions predominantly as a mediator of cell adhesion during early development of the mammalian telencephalon. Immunohistochemical analysis demonstrates that beta-catenin is localized, together with N-cadherin, to adhesion junctions at the apical lining of the neuroepithelium. The ablation of beta-catenin specifically from the forebrain leads to a disruption of apical adherens junctions and a breakdown of neuroepithelial structures. We show that beta-catenin-deficient neuroepithelial cells delaminate and undergo apoptosis. Newborn beta-catenin mutants lack the entire forebrain and anterior facial structures. Our data also indicate a lack of TCF/LEF-beta-catenin-dependent transcriptional activity in the telencephalon of Wnt reporter embryos. Together with the absence of nuclear beta-catenin, this finding suggests that canonical Wnt signalling is not active during early telencephalic development. In summary, we demonstrate that beta-catenin mediates cell-cell adhesion in the early telencephalon and is vital for maintaining the structural integrity of the neuroepithelium.

Characterization of the model for experimental testicular teratoma in 129/SvJ-mice

An animal model of experimental testicular teratoma has been established to study how a teratoma affects the host testis and how the host testis reacts against the teratoma. 129/SvJ-mice were used as experimental animals. To induce the experimental testicular teratoma, male gonadal ridges from 12-day-old 129/SvJ-mouse fetuses were grafted into the testes of adult mice for 1–12 weeks. The developing tumour was analysed by light and electron microscopy and by immunocytochemical localization of transcription factors SOX9 and c-kit, glial fibrillary acidic protein (GFAP) and type IV collagen. Testicular teratoma was observed in 36 out of 124 testes with implanted fetal gonadal ridges (frequency 29%). One spontaneous testicular teratoma was observed in this material from 70 male mice (1.5%). One week after implantation intracordal clusters of cells were seen in embryonic testicular cords of the graft as the first sign of testicular teratomas. Four weeks after implantation the embryonic testicular cords had totally disappeared from grafts with teratomas, and the tumour tissue had enlarged the testis and invaded the interstitium of the host testis. It consisted of solitary pieces of immature cartilage as well as of glial cells and of primitive neuroepithelium. Six to eight weeks after implantation the tumour tissue had expanded so that the enlarged testis could be detected by macroscopic enlargement of the scrotum. The testicular tissue of the host had practically disappeared, and only solitary disrupted seminiferous tubules of the host were seen surrounding the teratoma. Neuroepithelial structures of some teratomas cultured for 8 weeks had cells with a granular nucleus as a sign of obvious apoptosis. Eleven to 12 weeks after implantation the growth of the teratoma had stopped, and the histology corresponded to that of a mature cystic teratoma. GFAP, SOX9 and type IV collagen were strongly positive in some parts of the tumours cultured for 4 and 8 weeks, while only occasional c-kit-positive areas were observed in tumours cultured for 8 weeks. As conclusions: (1) the metastasizing capacity of the experimental testicular teratoma is very low during 12 weeks, but the behaviour of the tumour in the testicular tissue of the graft is invasive; (2) the growth of experimental testicular teratomas cease 6–8 weeks after implantation of the fetal gonadal ridges with the obvious apoptosis of the immature tissue components; (3) the model of experimental testicular teratoma in the mouse is suitable for studying how the teratoma affects the host testis and how the host testis reacts to teratoma. © 1999 Cancer Research Campaign

Characterization of the model for experimental testicular teratoma in 129/SvJ-mice

An animal model of experimental testicular teratoma has been established to study how a teratoma affects the host testis and how the host testis reacts against the teratoma. 129/SvJ-mice were used as experimental animals. To induce the experimental testicular teratoma, male gonadal ridges from 12-day-old 129/SvJ-mouse fetuses were grafted into the testes of adult mice for 1–12 weeks. The developing tumour was analysed by light and electron microscopy and by immunocytochemical localization of transcription factors SOX9 and c-kit, glial fibrillary acidic protein (GFAP) and type IV collagen. Testicular teratoma was observed in 36 out of 124 testes with implanted fetal gonadal ridges (frequency 29%). One spontaneous testicular teratoma was observed in this material from 70 male mice (1.5%). One week after implantation intracordal clusters of cells were seen in embryonic testicular cords of the graft as the first sign of testicular teratomas. Four weeks after implantation the embryonic testicular cords had totally disappeared from grafts with teratomas, and the tumour tissue had enlarged the testis and invaded the interstitium of the host testis. It consisted of solitary pieces of immature cartilage as well as of glial cells and of primitive neuroepithelium. Six to eight weeks after implantation the tumour tissue had expanded so that the enlarged testis could be detected by macroscopic enlargement of the scrotum. The testicular tissue of the host had practically disappeared, and only solitary disrupted seminiferous tubules of the host were seen surrounding the teratoma. Neuroepithelial structures of some teratomas cultured for 8 weeks had cells with a granular nucleus as a sign of obvious apoptosis. Eleven to 12 weeks after implantation the growth of the teratoma had stopped, and the histology corresponded to that of a mature cystic teratoma. GFAP, SOX9 and type IV collagen were strongly positive in some parts of the tumours cultured for 4 and 8 weeks, while only occasional c-kit-positive areas were observed in tumours cultured for 8 weeks. As conclusions: (1) the metastasizing capacity of the experimental testicular teratoma is very low during 12 weeks, but the behaviour of the tumour in the testicular tissue of the graft is invasive; (2) the growth of experimental testicular teratomas cease 6–8 weeks after implantation of the fetal gonadal ridges with the obvious apoptosis of the immature tissue components; (3) the model of experimental testicular teratoma in the mouse is suitable for studying how the teratoma affects the host testis and how the host testis reacts to teratoma.

In vitro-generated neural precursors participate in mammalian brain development.

During embryogenesis, pluripotent stem cells segregate into daughter lineages of progressively restricted developmental potential. In vitro, this process has been mimicked by the controlled differentiation of embryonic stem cells into neural precursors. To explore the developmental potential of these cell-culture-derived precursors in vivo, we have implanted them into the ventricles of embryonic rats. The transplanted cells formed intraventricular neuroepithelial structures and migrated in large numbers into the brain tissue. Embryonic-stem-cell-derived neurons, astrocytes, and oligodendrocytes incorporated into telencephalic, diencephalic, and mesencephalic regions and assumed phenotypes indistinguishable from neighboring host cells. These observations indicate that entirely in vitro-generated neural precursors are able to respond to environmental signals guiding cell migration and differentiation and have the potential to reconstitute neuronal and glial lineages in the central nervous system.

An immunohistochemical characterization of the primitive and maturing neuroepithelial components in the OTT-6050 transplantable mouse teratoma.

The neuroepithelial component of the OTT-6050 mouse teratoma has previously been characterized as an experimental system for the study of differentiation and cytologic maturation in embryonal tumours of the human central nervous system. A number of transplantable tumours composed of primitive stem cells and of a neuroepithelial component displaying a spectrum of differentiation were previously produced by centrifugal elutriation of the dissociated OTT-6050 teratoma. These tumours have provided a reproducible cell population that has permitted the study of both the early and later stages of neoplastic neurocytogenesis. The purpose of the present study was to detect, by immunohistochemistry, the earliest stages of neurocytogenesis in these tumours as shown by the expression of neuron-associated microtubule proteins. This was correlated to the appearance and localization of other markers associated with neuronal and glial differentiation. The primitive neuroepithelial structures resembling neural tubes (medulloepithelial rosettes) contained single or small groups of cells which reacted with the monoclonal antibody TUJ1, specific for the neuron-associated class III beta-tubulin isotype. Immature neuroblasts and maturing polar neurons also showed immunoreactivity with TUJ1, whereas reactivity for microtubule-associated protein 2 (MAP2), tau, the 200 kilodalton isoform of neurofilament protein, neuron-specific enolase and synaptophysin was primarily seen in maturing neurons. By comparison, both medulloepithelial and ependymoblastic rosettes, neuroblasts and glial cells were immunopositive with monoclonal antibody TU27, which defines an antigenic site shared by most mammalian beta-tubulin isotypes. Astroglia were reactive with antisera to glial fibrillary acidic and S-100 proteins, but not with monoclonal antibody (MAb) TUJ1, or with MAbs to the other neuron-associated cytoskeletal proteins, MAP2, tau and the 200 kilodalton subunit of neurofilament protein. Our findings suggest that (1) expression of the class III beta-tubulin isotype is an early event during neoplastic neurocytogenesis, (2) this isotype is subsequently preserved in maturing neuronal populations, and (3) it is not present at detectable levels in stem cells or glial cells. The observation that morphologically undifferentiated neuroepithelial cells express a neuron-associated beta-tubulin isotype signifies the value of examining tubulin isotype expression in the characterization of normal and neoplastic neuroepithelial differentiation.

Whole-body Autoradiography of [3H]Dihydrostreptomycin in Guinea Pigs and Rats: The Labelling of the Inner Ear in Relation to Other Tissues

[3H]Dihydrostreptomycin was given intramuscularly to young pigmented guinea pigs and rats. Whole-body autoradiography, combined with densitometric measurement of the blackening of the autoradiograms, and liquid scintillation counting were used to determine the levels of radioactivity in the inner ear in relation to blood and other tissues. It was found that there was an accumulation of radioactivity in the perilymph of both the cochlear and vestibular parts of the labyrinth. The labelling of the endolymph was weak. The levels of radioactivity in the membranous linings of the labyrinth including the areas covered with the neuroepithelial structures, were about the same as in the perilymph. The general distribution pictures were characterized by a localization of radioactivity in extracellular tissues, such as cartilages and connective tissues and by strong labelling of the kidney cortex. The preferential uptake in the perilymph indicates a route by which the inner ear hair cells can be exposed to high levels of aminoglycoside antibiotics.

Origin of the fast oscillation in the electroretinogram of the macaque

To investigate the origin of the fast oscillation, a phenomenon in the electroretinogram evoked with stimulus frequencies of about 8 mHz (a period time of about 2 min), we recorded responses from retina and pigment epithelium in the macaque. Micropipettes were placed in the subretinal space and in the vitreous close to the retina; the reference electrode was in the orbit behind the eye. Thus, simultaneous recordings were obtained of the trans-epithelial, the trans-retinal and the trans-tissue (vitreal) potential. At 10 mHz the trans-retinal and the trans-epithelial responses are of about equal magnitude but of opposite phase, resulting in a small and rather variable vitreal potential. The origin of the fast oscillation evoked with repetitive stimuli lies in subtle differences between retinal and pigment epithelial potentials, in which a pigment epithelial event plays an important role. For single stimuli lasting 60 s again the trans-epithelial and trans-retinal responses were of equal magnitude and opposite polarity. The epithelial responses were found to return more quickly towards the baseline than the retinal responses. In vitreal recordings this causes a trough between the c-wave and the light peak which is referred to as the “trough” fast oscillation. Most of the “trough” fast oscillation is caused by a pigment epithelial event. In view of the complexity of the fast oscillation evoked with repetitive stimuli it might be difficult to relate pathology to specific neuro-epithelial structures.

Temporal bone studies in anencephaly.

The principal anatomical and histological features of the temporal bones of three anencephalics are described, one a twin-headed monster, with four temporal bones. These may be summarized as follows: Malformation of ossicles. Mondini type malformation of the cochlea. Occasionally cochlear hydrops or collapse of Reissner's membrane, following apparently on its rupture. Distension of the vestibular labyrinth and oedema of the perilymphatic spaces and membranes. Rupture of the saccular wall with 'sealing off' and repair of the tears and gaps by coagulated lymph material. Fibrous obliteration of the internal auditory meatus containing scanty nerves and neurones. Geniculate ganglion and facial nerve present and appear to be normally developed. The neuro-epithelial structures were well developed despite the total or partial absence of the central nervous system. The temporal bones of anencephalics offer an excellent source of comparative anatomy for the study of the pathology of Menière's disease and sensorineural lesions.