scholarly journals Aquaporin-6 Expression in the Cochlear Sensory Epithelium Is Downregulated by Salicylates

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Paola Perin ◽  
Simona Tritto ◽  
Laura Botta ◽  
Jacopo Maria Fontana ◽  
Giulia Gastaldi ◽  
...  
Keyword(s):  
Inner Ear ◽  
Expression Pattern ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Rt Pcr ◽  
Supporting Cells ◽  
Sensory Epithelia ◽  
Mechanical Compliance

We characterize the expression pattern of aquaporin-6 in the mouse inner ear by RT-PCR and immunohistochemistry. Our data show that in the inner ear aquaporin-6 is expressed, in both vestibular and acoustic sensory epithelia, by the supporting cells directly contacting hair cells. In particular, in the Organ of Corti, expression was strongest in Deiters' cells, which provide both a mechanical link between outer hair cells (OHCs) and the Organ of Corti, and an entry point for ion recycle pathways. Since aquaporin-6 is permeable to both water and anions, these results suggest its possible involvement in regulating OHC motility, directly through modulation of water and chloride flow or by changing mechanical compliance in Deiters' cells. In further support of this role, treating mice with salicylates, which impair OHC electromotility, dramatically reduced aquaporin-6 expression in the inner ear epithelia but not in control tissues, suggesting a role for this protein in modulating OHCs' responses.

The developing organ of Corti contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1041-1053 ◽  
Author(s):  
M.W. Kelley ◽  
X.M. Xu ◽  
M.A. Wagner ◽  
M.E. Warchol ◽  
J.T. Corwin
Keyword(s):  
Retinoic Acid ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Supporting Cells ◽  
Embryonic Mouse ◽  
Inner Hair Cells ◽  
Sensory Epithelia

The mammalian organ of Corti has one of the most highly ordered patterns of cells in any vertebrate sensory epithelium. A single row of inner hair cells and three or four rows of outer hair cells extend along its length. The factors that regulate the formation of this strict pattern are unknown. In order to determine whether retinoic acid plays a role during the development of the organ of Corti, exogenous retinoic acid was added to embryonic mouse cochleae in vitro. Exogenous retinoic acid significantly increased the number of cells that developed as hair cells and resulted in large regions of supernumerary hair cells and supporting cells containing two rows of inner hair cells and up to 11 rows of outer hair cells. The effects of retinoic acid were dependent on concentration and on the timing of its addition. Western blot analysis indicated that cellular retinoic acid binding protein (CRABP) was present in the sensory epithelium of the embryonic cochlea. The amount of CRABP apparently increased between embryonic day 14 and postnatal day 1, but CRABP was not detectable in sensory epithelia from adults. A retinoic acid reporter cell line was used to demonstrate that retinoic acid was also present in the developing organ of Corti between embryonic day 14 and postnatal day 1, and was also present in adult cochleae at least in the vicinity of the modiolus. These results suggest that retinoic acid is involved in the normal development of the organ of Corti and that the effect of retinoic acid may be to induce a population of prosensory cells to become competent to differentiate as hair cells and supporting cells.

scholarly journals Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Sung-Ho Huh ◽  
Mark E Warchol ◽  
David M Ornitz
Keyword(s):  
Growth Factors ◽  
Hair Cells ◽  
Fibroblast Growth Factors ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Feedback Mechanism ◽  
Outer Hair Cells ◽  
Fibroblast Growth ◽  
Supporting Cells ◽  
Fgf Receptor

The sensory and supporting cells (SCs) of the organ of Corti are derived from a limited number of progenitors. The mechanisms that regulate the number of sensory progenitors are not known. Here, we show that Fibroblast Growth Factors (FGF) 9 and 20, which are expressed in the non-sensory (Fgf9) and sensory (Fgf20) epithelium during otic development, regulate the number of cochlear progenitors. We further demonstrate that Fgf receptor (Fgfr) 1 signaling within the developing sensory epithelium is required for the differentiation of outer hair cells and SCs, while mesenchymal FGFRs regulate the size of the sensory progenitor population and the overall cochlear length. In addition, ectopic FGFR activation in mesenchyme was sufficient to increase sensory progenitor proliferation and cochlear length. These data define a feedback mechanism, originating from epithelial FGF ligands and mediated through periotic mesenchyme that controls the number of sensory progenitors and the length of the cochlea.

Ionic Currents and Electromotility in Inner Ear Hair Cells From Humans

1998 ◽  
Vol 79 (4) ◽  
pp. 2235-2239 ◽  
Author(s):  
John S. Oghalai ◽  
Jeffrey R. Holt ◽  
Takashi Nakagawa ◽  
Thomas M. Jung ◽  
Newton J. Coker ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Ionic Currents ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Sensory Receptor ◽  
Surgical Removal ◽  
Type I ◽  
Vestibular Hair Cells ◽  
Sensory Receptor Cells

Oghalai, John S., Jeffrey R. Holt, Takashi Nakagawa, Thomas M. Jung, Newton J. Coker, Herman A. Jenkins, Ruth Anne Eatock, and William E. Brownell. Ionic currents and electromotility in inner ear hair cells from humans. J. Neurophysiol. 79: 2235–2239, 1998. The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.

Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3381-3391 ◽  
Author(s):  
T. Schimmang ◽  
L. Minichiello ◽  
E. Vazquez ◽  
I. San Jose ◽  
F. Giraldez ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Catalytic Domain ◽  
Sensory System ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Developmental Study ◽  
Inner Hair Cells ◽  
Vestibular Neurons ◽  
Cochlear Neurons

The trkB and trkC genes are expressed during the formation of the vestibular and auditory system. To elucidate the function of trkB and trkC during this process, we have analysed mice carrying a germline mutation in the tyrosine kinase catalytic domain of these genes. Neuroanatomical analysis of homozygous mutant mice revealed neuronal deficiencies in the vestibular and cochlear ganglia. In trkB (−/−) animals vestibular neurons and a subset of cochlear neurons responsible for the innervation of outer hair cells were drastically reduced. The peripheral targets of the respective neurons showed severe innervation defects. A comparative analysis of ganglia from trkC (−/−) mutants revealed a moderate reduction of vestibular neurons and a specific loss of cochlear neurons innervating inner hair cells. No nerve fibres were detected in the sensory epithelium containing inner hair cells. A developmental study of trkB (−/−) and trkC (−/−) mice showed that some vestibular and cochlear fibres initially reached their peripheral targets but failed to maintain innervation and degenerated. TrkB and TrkC receptors are therefore required for the survival of specific neuronal populations and the maintenance of target innervation in the peripheral sensory system of the inner ear.

p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1581-1590 ◽  
Author(s):  
P. Chen ◽  
N. Segil
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Inner Ear ◽  
Hair Cells ◽  
Cellular Proliferation ◽  
Adult Life ◽  
Organ Of Corti ◽  
Morphological Development ◽  
Supporting Cells ◽  
P27 Kip1

Strict control of cellular proliferation is required to shape the complex structures of the developing embryo. The organ of Corti, the auditory neuroepithelium of the inner ear in mammals, consists of two types of terminally differentiated mechanosensory hair cells and at least four types of supporting cells arrayed precisely along the length of the spiral cochlea. In mice, the progenitors of greater than 80% of both hair cells and supporting cells undergo their terminal division between embryonic day 13 (E13) and E14. As in humans, these cells persist in a non-proliferative state throughout the adult life of the animal. Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. p27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells. In wild-type animals, p27(Kip1) expression is downregulated during subsequent hair cell differentiation, but it persists at high levels in differentiated supporting cells of the mature organ of Corti. In mice with a targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell progenitors continues after E14, leading to the appearance of supernumerary hair cells and supporting cells. In the absence of p27(Kip1), mitotically active cells are still observed in the organ of Corti of postnatal day 6 animals, suggesting that the persistence of p27(Kip1) expression in mature supporting cells may contribute to the maintenance of quiescence in this tissue and, possibly, to its inability to regenerate. Homozygous mutant mice are severely hearing impaired. Thus, p27(Kip1) provides a link between developmental control of cell proliferation and the morphological development of the inner ear.

scholarly journals Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear

2019 ◽  
Vol 379 (3) ◽  
pp. 459-471 ◽  
Author(s):  
Lejo Johnson Chacko ◽  
Consolato Sergi ◽  
Theresa Eberharter ◽  
Jozsef Dudas ◽  
Helge Rask-Andersen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Inner Ear ◽  
Hair Cells ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Receptor Expression ◽  
Cell Phenotype ◽  
Type I

AbstractExpression patterns of transcription factors leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), transforming growth factor-β-activated kinase-1 (TAK1), SRY (sex-determining region Y)-box 2 (SOX2), and GATA binding protein 3 (GATA3) in the developing human fetal inner ear were studied between the gestation weeks 9 and 12. Further development of cochlear apex between gestational weeks 11 and 16 (GW11 and GW16) was examined using transmission electron microscopy. LGR5 was evident in the apical poles of the sensory epithelium of the cochlear duct and the vestibular end organs at GW11. Immunostaining was limited to hair cells of the organ of Corti by GW12. TAK1 was immune positive in inner hair cells of the organ of Corti by GW12 and colocalized with p75 neurotrophic receptor expression. Expression for SOX2 was confined primarily to the supporting cells of utricle at the earliest stage examined at GW9. Intense expression for GATA3 was presented in the cochlear sensory epithelium and spiral ganglia at GW9. Expression of GATA3 was present along the midline of both the utricle and saccule in the zone corresponding to the striolar reversal zone where the hair cell phenotype switches from type I to type II. The spatiotemporal gradient of the development of the organ of Corti was also evident with the apex of the cochlea forming by GW16. It seems that highly specific staining patterns of several transcriptions factors are critical in guiding the genesis of the inner ear over development. Our findings suggest that the spatiotemporal gradient in cochlear development extends at least until gestational week 16.

scholarly journals Static length changes of cochlear outer hair cells can tune low-frequency hearing

2017 ◽  
Author(s):  
Nikola Ciganović ◽  
Rebecca L. Warren ◽  
Batu Keçeli ◽  
Stefan Jacob ◽  
Anders Fridberger ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Frequency Selectivity ◽  
Apical Region ◽  
Low Frequencies ◽  
Inner Hair Cells ◽  
Length Changes ◽  
The Brain

AbstractThe cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organ’s motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings.Author summaryOuter hair cells are highly specialized force producers inside the inner ear: they can change length when stimulated electrically. However, how exactly this electromotile effect contributes to the astonishing sensitivity and frequency selectivity of the inner ear has remained unclear. Here we show for the first time that static length changes of outer hair cells can sensitively regulate how much of a sound signal is passed on to the inner hair cells that forward the signal to the brain. Our analysis holds for the apical region of the inner ear that is responsible for detecting the low frequencies that matter most in speech and music. This shows a mechanisms for how frequency-selectivity can be achieved at low frequencies. It also opens a path for the efferent neural system to regulate hearing sensitivity.

Epithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti

2002 ◽  
Vol 59 (10) ◽  
pp. 1744-1757 ◽  
Author(s):  
B. Malgrange ◽  
M. Thiry ◽  
T. R. Van de Water ◽  
L. Nguyen ◽  
G. Moonen ◽  
...  
Keyword(s):  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Supporting Cells

scholarly journals Research Progress on Flat Epithelium of the Inner Ear

2020 ◽  
pp. 775-785
Author(s):  
L HE ◽  
J-Y GUO ◽  
K LIU ◽  
G-P WANG ◽  
S-S GONG
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Noise Exposure ◽  
Sensory Epithelium ◽  
Sensorineural Hearing ◽  
Research Progress ◽  
Supporting Cells ◽  
Mesenchymal Transition

Sensorineural hearing loss and vertigo, resulting from lesions in the sensory epithelium of the inner ear, have a high incidence worldwide. The sensory epithelium of the inner ear may exhibit extreme degeneration and is transformed to flat epithelium (FE) in humans and mice with profound sensorineural hearing loss and/or vertigo. Various factors, including ototoxic drugs, noise exposure, aging, and genetic defects, can induce FE. Both hair cells and supporting cells are severely damaged in FE, and the normal cytoarchitecture of the sensory epithelium is replaced by a monolayer of very thin, flat cells of irregular contour. The pathophysiologic mechanism of FE is unclear but involves robust cell division. The cellular origin of flat cells in FE is heterogeneous; they may be transformed from supporting cells that have lost some features of supporting cells (dedifferentiation) or may have migrated from the flanking region. The epithelial-mesenchymal transition may play an important role in this process. The treatment of FE is challenging given the severe degeneration and loss of both hair cells and supporting cells. Cochlear implant or vestibular prosthesis implantation, gene therapy, and stem cell therapy show promise for the treatment of FE, although many challenges remain to be overcome.

scholarly journals The Key Transcription Factor Expression in the Developing Vestibular and Auditory Sensory Organs: A Comprehensive Comparison of Spatial and Temporal Patterns

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Shaofeng Liu ◽  
Yunfeng Wang ◽  
Yongtian Lu ◽  
Wen Li ◽  
Wenjing Liu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Inner Ear ◽  
Hair Cells ◽  
Expression Patterns ◽  
Organ Of Corti ◽  
Sensory Organ ◽  
Sensory Organs ◽  
Supporting Cells ◽  
Cell Fate Decisions ◽  
Temporal And Spatial

Inner ear formation requires that a series of cell fate decisions and morphogenetic events occur in a precise temporal and spatial pattern. Previous studies have shown that transcription factors, including Pax2, Sox2, and Prox1, play important roles during the inner ear development. However, the temporospatial expression patterns among these transcription factors are poorly understood. In the current study, we present a comprehensive description of the temporal and spatial expression profiles of Pax2, Sox2, and Prox1 during auditory and vestibular sensory organ development in mice. Using immunohistochemical analyses, we show that Sox2 and Pax2 are both expressed in the prosensory cells (the developing hair cells), but Sox2 is later restricted to only the supporting cells of the organ of Corti. In the vestibular sensory organ, however, the Pax2 expression is localized in hair cells at postnatal day 7, while Sox2 is still expressed in both the hair cells and supporting cells at that time. Prox1 was transiently expressed in the presumptive hair cells and developing supporting cells, and lower Prox1 expression was observed in the vestibular sensory organ compared to the organ of Corti. The different expression patterns of these transcription factors in the developing auditory and vestibular sensory organs suggest that they play different roles in the development of the sensory epithelia and might help to shape the respective sensory structures.

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