scholarly journals SoxC transcription factors are essential for the development of the inner ear

2015 ◽  
Vol 112 (45) ◽  
pp. 14066-14071 ◽  
Author(s):  
Ksenia Gnedeva ◽  
A. J. Hudspeth
Keyword(s):  
Transcription Factors ◽  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Supporting Cell ◽  
Sensory Epithelia ◽  
Enhanced Expression ◽  
Mechanosensory Receptors

Hair cells, the mechanosensory receptors of the inner ear, underlie the senses of hearing and balance. Adult mammals cannot adequately replenish lost hair cells, whose loss often results in deafness or balance disorders. To determine the molecular basis of this deficiency, we investigated the development of a murine vestibular organ, the utricle. Here we show that two members of the SoxC family of transcription factors, Sox4 and Sox11, are down-regulated after the epoch of hair cell development. Conditional ablation of SoxC genes in vivo results in stunted sensory organs of the inner ear and loss of hair cells. Enhanced expression of SoxC genes in vitro conversely restores supporting cell proliferation and the production of new hair cells in adult sensory epithelia. These results imply that SoxC genes govern hair cell production and thus advance these genes as targets for the restoration of hearing and balance.

Hair cell development in vivo and in vitro: Analysis by using a monoclonal antibody specific to hair cells in the chick inner ear

2002 ◽  
Vol 445 (2) ◽  
pp. 176-198
Author(s):  
Kenji Kondo ◽  
Hiroshi Sagara ◽  
Kazushige Hirosawa ◽  
Kimitaka Kaga ◽  
Satsuki Matsushima ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Development ◽  
Vitro Analysis ◽  
In Vitro Analysis

Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3935-3946 ◽  
Author(s):  
M. Xiang ◽  
W.Q. Gao ◽  
T. Hasson ◽  
J.J. Shin
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Loss ◽  
Supporting Cell ◽  
Sensory Epithelium ◽  
Cell Phenotype ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia ◽  
And Migration

Mutations in the POU domain gene Brn-3c causes hearing impairment in both the human and mouse as a result of inner ear hair cell loss. We show here that during murine embryogenesis, Brn-3c is expressed in postmitotic cells committed to hair cell phenotype but not in mitotic progenitors in the inner ear sensory epithelium. In developing auditory and vestibular sensory epithelia of Brn-3c−/− mice, hair cells are found to be generated and undergo initial differentiation as indicated by their morphology, laminar position and expression of hair cell markers, including myosins VI and VIIa, calretinin and parvalbumin. However, a small number of hair cells are anomalously retained in the supporting cell layer in the vestibular sensory epithelia. Furthermore, the initially differentiated hair cells fail to form stereociliary bundles and degenerate by apoptosis in the Brn-3c−/− mice. These data indicate a crucial role for Brn-3c in maturation, survival and migration of hair cells, but not in proliferation or commitment of hair cell progenitors.

scholarly journals ERBB 2 signaling drives supporting cell proliferation in vitro and apparent supernumerary hair cell formation in vivo in the neonatal mouse cochlea

2018 ◽  
Vol 48 (10) ◽  
pp. 3299-3316 ◽  
Author(s):  
Jingyuan Zhang ◽  
Quan Wang ◽  
Dunia Abdul‐Aziz ◽  
Jonelle Mattiacio ◽  
Albert S. B. Edge ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hair Cell ◽  
Cell Formation ◽  
Supporting Cell ◽  
Neonatal Mouse ◽  
Proliferation In Vitro

scholarly journals Calcium Modulates the Frequency and Amplitude of Spontaneous Otoacoustic Emissions in the Bobtail Skink

2004 ◽  
Vol 92 (5) ◽  
pp. 2685-2693 ◽  
Author(s):  
Geoffrey A. Manley ◽  
Ulrike Sienknecht ◽  
Christine Köppl
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Otoacoustic Emissions ◽  
Calcium Concentration ◽  
Chelating Agent ◽  
Lizard Species ◽  
Spontaneous Otoacoustic Emissions ◽  
Active Processes

Active processes in the inner ear of lizards can be monitored using spontaneous otoacoustic emissions (SOAE) measured outside the eardrum. In the Australian bobtail lizard, SOAE are generated by an active motility process in the hair-cell bundle. This mechanism has been shown to be sensitive to the calcium-chelating agent 1,2-bis(o-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid and is presumed to be related to the calcium-sensitive transduction-channel motor implicated in other nonmammalian hair cell systems. In studies of frog saccular and turtle auditory papillar hair cells in vitro, the frequency and amplitude of bundle oscillations depend on the concentration of calcium in the bathing solutions. In the present study, the calcium concentration in the endolymph was changed in vivo in the Australian bobtail lizard Tiliqua rugosa, and SOAE were monitored. Glass pipettes with large tips and containing different calcium concentrations in their fluids were introduced into scala media, and their contents were allowed to passively flow into the endolymph. Low calcium concentrations resulted in a downward shift in the frequency of SOAE spectral peaks and generally an increase in their amplitudes. Calcium concentrations >2 mM resulted in increases in frequency of SOAE peaks and generally a loss in amplitude. These frequency shifts were consistent with in vitro data on the frequencies and amplitudes of spontaneous oscillation of hair cell bundles and thus also implicate calcium ions in the generation of active motility in nonmammalian hair cells. The data also suggest that in this lizard species, the ionic calcium concentration in the cochlear endolymph is ≥1 mM.

scholarly journals Vestibular and Auditory Hair Cell Regeneration Following Targeted Ablation of Hair Cells With Diphtheria Toxin in Zebrafish

2021 ◽  
Vol 15 ◽  
Author(s):  
Erin Jimenez ◽  
Claire C. Slevin ◽  
Luis Colón-Cruz ◽  
Shawn M. Burgess
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Lateral Line ◽  
Hair Cells ◽  
Diphtheria Toxin ◽  
Adult Zebrafish ◽  
Hair Cell Regeneration ◽  
Cell Ablation ◽  
Aquatic Vertebrates

Millions of Americans experience hearing or balance disorders due to loss of hair cells in the inner ear. The hair cells are mechanosensory receptors used in the auditory and vestibular organs of all vertebrates as well as the lateral line systems of aquatic vertebrates. In zebrafish and other non-mammalian vertebrates, hair cells turnover during homeostasis and regenerate completely after being destroyed or damaged by acoustic or chemical exposure. However, in mammals, destroying or damaging hair cells results in permanent impairments to hearing or balance. We sought an improved method for studying hair cell damage and regeneration in adult aquatic vertebrates by generating a transgenic zebrafish with the capacity for targeted and inducible hair cell ablation in vivo. This model expresses the human diphtheria toxin receptor (hDTR) gene under the control of the myo6b promoter, resulting in hDTR expressed only in hair cells. Cell ablation is achieved by an intraperitoneal injection of diphtheria toxin (DT) in adult zebrafish or DT dissolved in the water for larvae. In the lateral line of 5 days post fertilization (dpf) zebrafish, ablation of hair cells by DT treatment occurred within 2 days in a dose-dependent manner. Similarly, in adult utricles and saccules, a single intraperitoneal injection of 0.05 ng DT caused complete loss of hair cells in the utricle and saccule by 5 days post-injection. Full hair cell regeneration was observed for the lateral line and the inner ear tissues. This study introduces a new method for efficient conditional hair cell ablation in adult zebrafish inner ear sensory epithelia (utricles and saccules) and demonstrates that zebrafish hair cells will regenerate in vivo after this treatment.

scholarly journals Conserved and Divergent Principles of Planar Polarity Revealed by Hair Cell Development and Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Michael R. Deans
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Model Organism ◽  
Vestibular Function ◽  
Sensory Receptor ◽  
Apical Surface ◽  
Planar Polarity ◽  
Vestibular Hair Cells ◽  
Sensory Epithelia

Planar polarity describes the organization and orientation of polarized cells or cellular structures within the plane of an epithelium. The sensory receptor hair cells of the vertebrate inner ear have been recognized as a preeminent vertebrate model system for studying planar polarity and its development. This is principally because planar polarity in the inner ear is structurally and molecularly apparent and therefore easy to visualize. Inner ear planar polarity is also functionally significant because hair cells are mechanosensors stimulated by sound or motion and planar polarity underlies the mechanosensory mechanism, thereby facilitating the auditory and vestibular functions of the ear. Structurally, hair cell planar polarity is evident in the organization of a polarized bundle of actin-based protrusions from the apical surface called stereocilia that is necessary for mechanosensation and when stereociliary bundle is disrupted auditory and vestibular behavioral deficits emerge. Hair cells are distributed between six sensory epithelia within the inner ear that have evolved unique patterns of planar polarity that facilitate auditory or vestibular function. Thus, specialized adaptations of planar polarity have occurred that distinguish auditory and vestibular hair cells and will be described throughout this review. There are also three levels of planar polarity organization that can be visualized within the vertebrate inner ear. These are the intrinsic polarity of individual hair cells, the planar cell polarity or coordinated orientation of cells within the epithelia, and planar bipolarity; an organization unique to a subset of vestibular hair cells in which the stereociliary bundles are oriented in opposite directions but remain aligned along a common polarity axis. The inner ear with its complement of auditory and vestibular sensory epithelia allows these levels, and the inter-relationships between them, to be studied using a single model organism. The purpose of this review is to introduce the functional significance of planar polarity in the auditory and vestibular systems and our contemporary understanding of the developmental mechanisms associated with organizing planar polarity at these three cellular levels.

scholarly journals How to build a fast and highly sensitive sound detector that remains robust to temperature shifts

2019 ◽  
Author(s):  
Minghui Chen ◽  
Henrique von Gersdorff
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Auditory Information ◽  
Temperature Changes ◽  
Temporal Precision ◽  
Auditory Nerves ◽  
Afferent Fibers ◽  
Vesicle Exocytosis

AbstractFrogs must have sharp hearing abilities during the warm summer months to successfully find mating partners. This study aims to understand how frog hair cell ribbon-type synapses preserve both sensitivity and temporal precision during temperature changes. We performedin vitropatch-clamp recordings of hair cells and their afferent fibers in bullfrog amphibian papillae under room (23-25°C) and high (30-33°C) temperature. Afferent fibers exhibited a wide heterogeneity in membrane input resistance (Rin) from 100 MΩ to 1000 MΩ, which may contribute to variations in spike threshold and firing frequency. At higher temperatures, most fibers increased their frequency of action potential firing due to an increase in spontaneous EPSC frequencies. Hair cell resting membrane potential (Vrest) remained surprisingly stable during temperature increases, although both inward Ca2+current and outward K+current increased in amplitude. This increase in Ca2+current may explain the higher spontaneous EPSC frequencies. The larger “leak currents” at Vrestlowered Rinand produced higher electrical resonant frequencies. However, lower Rinshould decrease sensitivity to sound detection via smaller receptor potentials. Using membrane capacitance measurements, we suggest that hair cells can partially compensate for this reduced sensitivity by increasing exocytosis efficiency and the size of the readily releasable pool of synaptic vesicles. Furthermore, paired recordings of hair cells and their afferent fibers showed that synaptic delays become shorter and multivesicular release becomes more synchronous at higher temperatures, which should improve temporal precision. Altogether, our results explain many previousin vivoobservations on the temperature dependence of spikes in auditory nerves.Significance StatementThe vertebrate inner ear detects and transmits auditory information over a broad dynamic range of sound frequency and intensity. It achieves remarkable sensitivity to soft sounds and precise frequency selectivity. How does the ear of cold-blooded vertebrates maintain its performance level as temperature changes? More specifically, how does the hair cell to afferent fiber synapse in bullfrog amphibian papilla adjust to a wide range of physiological temperatures without losing its sensitivity and temporal fidelity to sound signals? This study usesin vitroexperiments to reveal the biophysical mechanisms that explain many observations made fromin vivoauditory nerve fiber recordings. We find that higher temperature facilitates vesicle exocytosis and electrical tuning to higher sound frequencies, which benefits sensitivity and selectivity.

scholarly journals Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Tomoko Hyakumura ◽  
Stuart McDougall ◽  
Sue Finch ◽  
Karina Needham ◽  
Mirella Dottori ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cochlear Nucleus ◽  
Cell Types ◽  
Quantitative Evidence ◽  
Brainstem Slice

Stem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed on target cell types. Nascent contacts between stem cells and hair cells were immunopositive for both synapsin I and VGLUT1, closely resembling expression of these puncta in endogenous postnatal auditory neurons and control cocultures. When hPSCs were cocultured with cochlear nucleus brainstem slice, significantly greater numbers of VGLUT1 puncta were observed in comparison to slice alone. New VGLUT1 puncta in cocultures with cochlear nucleus slice were not significantly different in size, only in quantity. This experimentation describes new coculture models for assessing auditory regeneration using well-characterised hPSC-derived neurons and highlights useful methods to quantify the extent of innervation on different cell types in the inner ear and brainstem.

The Effect of Tgfß-2 on Inner Ear Development: Light and Electron Microscopy Observations

1997 ◽  
Vol 3 (S2) ◽  
pp. 173-174
Author(s):  
R. Friedman ◽  
N. Paradies ◽  
S. Wert ◽  
T. Doetschman ◽  
E.L. Cardell
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Light And Electron Microscopy ◽  
Membranous Labyrinth ◽  
Ear Development ◽  
Inner Ear Development

Transforming growth factor beta (TGFß) genes are linked to a variety of developmental processes and are the subject of in vivo and in vitro transgene research studies. We are evaluating TGFß-2 effects on mouse inner ear development, with emphasis on the cochlear duct (CD), by comparing plastic sections of intact inner ears from developmental day (D) 16.5,18.5 and 19.5 littermates with wildtype (+/+), heterozygous (+/−) and mutant (−/−) TGFß-2 genotypes as determined by polymerase chain reaction analysis of tail digests. Auditory and vestibular organs of all D16.5 mice appear similar: membranous labyrinth epithelium varies from simple cuboidal/low columnar to pseudostratified/stratified columnar. Surrounding mesenchyme varies in cell density regionally, the most cellular mesenchyme underlies areas of sensory epithelium. Sparse mesenchymal cell distribution in the vestibule and basal CD indicates sites of perilymph channel formation. The spiral and vestibular ganglia and their unmyelinated fibers are prominent. Otoconia and hair cells are present in the utricle (U) and saccule (S) maculae; hair cells are less easily identifiable in the CD.

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