Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear

An early and crucial event in vertebrate inner ear development is the acquisition of axial identities that in turn dictate the positions of all subsequent inner ear components. Here, we focus on the role of the hindbrain in establishment of inner ear axes and show that axial specification occurs well after otic placode formation in chicken. Anteroposterior (AP) rotation of the hindbrain prior to specification of this axis does not affect the normal AP orientation and morphogenesis of the inner ear. By contrast, reversing the dorsoventral (DV) axis of the hindbrain results in changing the DV axial identity of the inner ear. Expression patterns of several ventrally expressed otic genes such as NeuroD, Lunatic fringe (Lfng) and Six1 are shifted dorsally, whereas the expression pattern of a normally dorsal-specific gene, Gbx2, is abolished. Removing the source of Sonic Hedgehog (SHH) by ablating the floor plate and/or notochord, or inhibiting SHH function using an antibody that blocks SHH bioactivity results in loss of ventral inner ear structures. Our results indicate that SHH, together with other signals from the hindbrain, are important for patterning the ventral axis of the inner ear. Taken together, our studies suggest that tissue(s) other than the hindbrain confer AP axial information whereas signals from the hindbrain are necessary and sufficient for the DV axial patterning of the inner ear

Determining the Location of GABA Receptor mRNA Transcripts in \u3cem\u3eDanio rerio\u3c/em\u3e

-aminobutyric acid (GABA) is a neurotransmitter that has been shown to be present in the inner ear. GABA binds to two classes of GABA receptors (GABARs): GABAARs are pentameric ion channels (isoforms include: 1-6, β 1-3, 1-3, 1-3, , , and ); GABABRs are G-protein coupled receptors (isoforms include: 1a, 1b, and 2). Studies have shown that GABAAR and GABABR transcripts are located in the inner ear but their function is not yet fully understood. This is in part due to access to the inner ear being very limited. Our experiments are designed to further our understanding of the role of GABA in the inner ear by utilizing the lateral line of the zebrafish

Audio-vestibular symptoms in systemic autoimmune diseases

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing loss shows a good response to corticosteroid therapy that may lead to near-complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness can be found in patients with systemic autoimmune diseases; they often mimic primary inner ear disorders such as Menière’s disease and mainly affect both ears simultaneously. Awareness of inner ear involvement in systemic autoimmune diseases is essential for the good response shown to appropriate treatment. However, it is often misdiagnosed due to variable clinical presentation, limited knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of this review is to analyse available evidence, often only reported in the form of case reports due to the rarity of some of these conditions, of the different clinical presentations of audiological and vestibular symptoms in systemic autoimmune diseases

Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders

Development of a dynamic virtual reality model of the inner ear sensory system as a learning and demonstrating tool

In order to keep track of the position and motion of our body in space, nature has given us a fascinating and very ingenious organ, the inner ear. Each inner ear includes five biological sensors - three angular and two linear accelerometers - which provide the body with the ability to sense angular and linear motion of the head with respect to inertial space. The aim of this paper is to present a dynamic virtual reality model of these sensors. This model, implemented in Matlab/Simulink, simulates the rotary chair testing which is one of the tests carried out during a diagnosis of the vestibular system. High-quality 3D-animations linked to the Simulink model are created using the export of CAD models into Virtual Reality Modeling Language (VRML) files. This virtual environment shows not only the test but also the state of each sensor (excited or inhibited) in real time. Virtual reality is used as a tool of integrated learning of the dynamic behavior of the inner ear using ergonomic paradigm of user interactivity (zoom, rotation, mouse interaction,…). It can be used as a learning and demonstrating tool either in the medicine field - to understand the behavior of the sensors during any kind of motion - or in the aeronautical field to relate the inner ear functioning to some sensory illusions

Functional anatomy of the middle and inner ears of the red fox, in comparison to domestic dogs and cats

Anatomical middle and inner ear parameters are often used to predict hearing sensitivities of mammalian species. Given that ear morphology is substantially affected both by phylogeny and body size, it is interesting to consider whether the relatively small anatomical differences expected in related species of similar size have a noticeable impact on hearing. We present a detailed anatomical description of the middle and inner ears of the red fox Vulpes vulpes, a widespread, wild carnivore for which a behavioural audiogram is available. We compare fox ears to those of the well‐studied and similarly sized domestic dog and cat, taking data for dogs and cats from the literature as well as providing new measurements of basilar membrane (BM) length and hair cell numbers and densities in these animals. Our results show that the middle ear of the red fox is very similar to that of dogs. The most obvious difference from that of the cat is the lack of a fully formed bony septum in the bulla tympanica of the fox. The cochlear structures of the fox, however, are very like those of the cat, whereas dogs have a broader BM in the basal cochlea. We further report that the mass of the middle ear ossicles and the bulla volume increase with age in foxes. Overall, the ear structures of foxes, dogs and cats are anatomically very similar, and their behavioural audiograms overlap. However, the results of several published models and correlations that use middle and inner ear measurements to predict aspects of hearing were not always found to match well with audiogram data, especially when it came to the sharper tuning in the fox audiogram. This highlights that, although there is evidently a broad correspondence between structure and function, it is not always possible to draw direct links when considering more subtle differences between related species

Which GABA Receptors Are Expressed in the Zebrafish Lateral Line?

The presence of the neurotransmitter GABA in the mammalian inner ear is well established, yet its role in regulating inner ear cell function is less clear. We seek to understand the role of the GABA in the inner ear using the model organism zebrafish. Zebrafish possess a sense that humans do not: they can detect water movement with their lateral line system. Zebrafish sense water movement with cells that project out from the body of the fish into the environment. These so-called hair cells are remarkably similar to the sensory cells of the cochlea and semi-circular canals. Because they are on the outside of the zebrafish, and not behind a bony skull, lateral line hair cells are easily accessible to study. Therefore, we are determining if we can use the lateral line system to understand more about GABA in the inner ear. We have used RNA extraction and RT-PCR to detect the expression of 27 GABA-related genes in zebrafish. We have also identified a novel alternative exon in one isoform. Overall, our results suggest that the genes expressed in the lateral line are orthologs of genes expressed in the mammalian inner ear, and thus zebrafish appear to be an appropriate model organism with which to further study GABA function in the inner ear

The endocranial morphology and inner ear of the abelisaurid theropod Aucasaurus garridoi

A partial cranial endocast and right inner ear of the Cretaceous abelisaurid dinosaur Aucasaurus garridoi were digitally reconstructed from CT scans. The forebrain, midbrain, and hindbrain resemble the morphology described for the abelisaurids Majungasaurus and Indosaurus. However, Aucasaurus exhibits a floccular process that is relatively larger than that of Majungasaurus. In Aucasaurus the flocculus is enclosed in an 8-shaped floccular recess, similar in shape and size to that observed in Abelisaurus, suggesting that the two Patagonian taxa were capable of a slightly wider range of movements of the head. Here we describe the second inner ear known for the Abelisauridae. The labyrinth of the inner ear is similar in shape and size to the semicircular canals of Majungasaurus, although the lateral semicircular canal is shorter in Aucasaurus.Fil: Paulina Carabajal, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Provincia del Neuquén. Municipalidad de Plaza Huincul. Museo ; ArgentinaFil: Succar, Cecilia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Provincia del Neuquén. Municipalidad de Plaza Huincul. Museo ; Argentin

Molecular and functional characterization of gap junctions in the avian inner ear.

To analyze the fundamental role of gap junctions in the vertebrate inner ear, we examined molecular and functional characteristics of gap junctional communication (GJC) in the auditory and vestibular system of the chicken. By screening inner ear tissues for connexin isoforms using degenerate reverse transcription-PCR, we identified, in addition to chicken Cx43 (cCx43) and the inner-ear-specific cCx30, an as yet uncharacterized connexin predicted to be the ortholog of the mammalian Cx26. In situ hybridization indicated that cCx30 and cCx26 transcripts were both widely expressed in the cochlear duct and utricle in an overlapping pattern, suggesting coexpression of these isoforms similar to that in the mammalian inner ear. Immunohistochemistry demonstrated that cCx43 was present in gap junctions connecting supporting cells of the basilar papilla, in which its immunofluorescence colocalized with that of cCx30. However, cCx43 was absent from supporting cell gap junctions of the utricular macula. This variation in the molecular composition of gap junction plaques coincided with differences in the functional properties of GJC between the auditory and vestibular sensory epithelia. Fluorescence recovery after photobleaching, adapted to examine the diffusion of calcein in inner ear explants, revealed asymmetric communication pathways among supporting cells in the basilar papilla but not in the utricular macula. This study supports the hypothesis that the coexpression of Cx26/Cx30 is unique to gap junctions in the vertebrate inner ear. Furthermore, it demonstrates asymmetric GJC within the supporting cell population of the auditory sensory epithelium, which might mediate potassium cycling and/or intercellular signaling