scholarly journals Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Martin L Basch ◽  
Rogers M Brown ◽  
Hsin-I Jen ◽  
Fatih Semerci ◽  
Frederic Depreux ◽  
...  
Keyword(s):  
Hair Cell ◽  
Notch Signaling ◽  
Hair Cells ◽  
Sensory Cell ◽  
Organ Of Corti ◽  
Fine Tuning ◽  
Pharmacological Treatments ◽  
Cell Fates ◽  
Inner Hair Cells ◽  
Mouse Mutants

The signals that induce the organ of Corti and define its boundaries in the cochlea are poorly understood. We show that two Notch modifiers, Lfng and Mfng, are transiently expressed precisely at the neural boundary of the organ of Corti. Cre-Lox fate mapping shows this region gives rise to inner hair cells and their associated inner phalangeal cells. Mutation of Lfng and Mfng disrupts this boundary, producing unexpected duplications of inner hair cells and inner phalangeal cells. This phenotype is mimicked by other mouse mutants or pharmacological treatments that lower but not abolish Notch signaling. However, strong disruption of Notch signaling causes a very different result, generating many ectopic hair cells at the expense of inner phalangeal cells. Our results show that Notch signaling is finely calibrated in the cochlea to produce precisely tuned levels of signaling that first set the boundary of the organ of Corti and later regulate hair cell development.

scholarly journals Author response: Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates

2016 ◽  
Author(s):  
Martin L Basch ◽  
Rogers M Brown ◽  
Hsin-I Jen ◽  
Fatih Semerci ◽  
Frederic Depreux ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Sensory Cell ◽  
Organ Of Corti ◽  
Fine Tuning ◽  
Author Response ◽  
Cell Fates

Ultrastructural Cochlear Changes following Acoustic Hyperstimulation and Ototoxicity

1976 ◽  
Vol 85 (6) ◽  
pp. 740-751 ◽  
Author(s):  
David J. Lim
Keyword(s):  
Hair Cells ◽  
Sensory Cell ◽  
Ganglion Cells ◽  
Organ Of Corti ◽  
Acoustic Trauma ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Type I ◽  
Cell Degeneration ◽  
Inner Hair Cells

Using guinea pigs and chinchillas as experimental animals, modes and patterns of sensory cell damage by acoustic hyperstimulation and kanamycin intoxication were compared. In general, outer hair cells were more vulnerable to both acoustic trauma and ototoxicity (particularly in the basal turn) than inner hair cells. However, in kanamycin ototoxicity, the inner hair cells were more vulnerable in the apical coil. Nerve endings and nerve fibers generally were resistant to both acoustic trauma and kanamycin intoxication, and their degeneration appears to be secondary to the sensory cell degeneration. A large number of unmyelinated nerve fibers were seen in both the organ of Corti and the osseous spiral lamina even three months after the organ of Corti had been completely degenerated by ototoxicity. The total number of unmyelinated and myelinated nerve fibers in the osseous spiral lamina far exceeded the scanty surviving ganglion cells in Rosenthal's canal, indicating the possibility of regeneration of these fibers following kanamycin intoxication. The remaining few ganglion cells were mainly type II or type III cells, and a majority of the type I ganglion cells appeared to be degenerated. Signs of strial damage were observed in both acoustic trauma and ototoxicity, but their pattern did not correlate well with that of sensory cell degeneration.

A comparative study of surface preparations of the organ of Corti of the harp seal (Pagophilus groenlandicus Erxleben 1777) and the ringed seal (Pusa hispida). 1. Sensory cell population and density

1976 ◽  
Vol 54 (1) ◽  
pp. 1-9 ◽  
Author(s):  
F. Ramprashad ◽  
K. Ronald ◽  
J. Geraci ◽  
T. G. Smith
Keyword(s):  
Cell Population ◽  
Hair Cells ◽  
Sensory Cell ◽  
Organ Of Corti ◽  
Ringed Seal ◽  
Outer Hair Cells ◽  
Harp Seal ◽  
Sensory Cells ◽  
Unit Surface Area ◽  
Inner Hair Cells

The surface preparation technique was used to estimate the sensory cell population and density in the organ of Corti of seven harp seals and four ringed seals. The average total of inner hair cells for the harp seal was 3654 (3078–263) as compared with an average total of 3232 (3120–3354) in the ringed seal. The average total number of outer hair cells in the harp seal was 14 318 (12 173 – 15 709) as compared with an average total of 13 497 (12 903 – 14 894).The distribution of outer and inner hair cells showed an increase in density from base to apex. An increase in density of about 21% and 29% was observed in the inner hair cells of the ringed and harp seal. The increase in density for each row of outer hair cells was 21% in the harp seal and 17% in the ringed seal. The density of outer hair cells per unit surface area decreased from a maximum value at the base to about half its value at the apex.The average total sensory cells of seals exceeded the average total sensory cells of both man and dolphin but were within the range of variation of the human.

scholarly journals Inner hair cell stereocilia are embedded in the tectorial membrane

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Hakizimana ◽  
Anders Fridberger
Keyword(s):  
Electron Microscopy ◽  
Hair Cell ◽  
Mechanical Stimulation ◽  
Hair Cells ◽  
Viscous Drag ◽  
Tectorial Membrane ◽  
Inner Hair Cell ◽  
Inner Hair Cells ◽  
Inward Currents

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.

scholarly journals Disruption of Hars2 in Cochlear Hair Cells Causes Progressive Mitochondrial Dysfunction and Hearing Loss in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Pengcheng Xu ◽  
Longhao Wang ◽  
Hu Peng ◽  
Huihui Liu ◽  
Hongchao Liu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Mitochondrial Dysfunction ◽  
Hair Cells ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Hair Cell Loss ◽  
Progressive Hearing Loss ◽  
Cochlear Hair Cells ◽  
Inner Hair Cells

Mutations in a number of genes encoding mitochondrial aminoacyl-tRNA synthetases lead to non-syndromic and/or syndromic sensorineural hearing loss in humans, while their cellular and physiological pathology in cochlea has rarely been investigated in vivo. In this study, we showed that histidyl-tRNA synthetase HARS2, whose deficiency is associated with Perrault syndrome 2 (PRLTS2), is robustly expressed in postnatal mouse cochlea including the outer and inner hair cells. Targeted knockout of Hars2 in mouse hair cells resulted in delayed onset (P30), rapidly progressive hearing loss similar to the PRLTS2 hearing phenotype. Significant hair cell loss was observed starting from P45 following elevated reactive oxygen species (ROS) level and activated mitochondrial apoptotic pathway. Despite of normal ribbon synapse formation, whole-cell patch clamp of the inner hair cells revealed reduced calcium influx and compromised sustained synaptic exocytosis prior to the hair cell loss at P30, consistent with the decreased supra-threshold wave I amplitudes of the auditory brainstem response. Starting from P14, increasing proportion of morphologically abnormal mitochondria was observed by transmission electron microscope, exhibiting swelling, deformation, loss of cristae and emergence of large intrinsic vacuoles that are associated with mitochondrial dysfunction. Though the mitochondrial abnormalities are more prominent in inner hair cells, it is the outer hair cells suffering more severe cell loss. Taken together, our results suggest that conditional knockout of Hars2 in mouse cochlear hair cells leads to accumulating mitochondrial dysfunction and ROS stress, triggers progressive hearing loss highlighted by hair cell synaptopathy and apoptosis, and is differentially perceived by inner and outer hair cells.

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.

Comparing Sensory Organs to Define the Path for Hair Cell Regeneration

2019 ◽  
Vol 35 (1) ◽  
pp. 567-589 ◽  
Author(s):  
Nicolas Denans ◽  
Sungmin Baek ◽  
Tatjana Piotrowski
Keyword(s):  
Hair Cell ◽  
Olfactory Epithelium ◽  
Current Literature ◽  
Hair Cells ◽  
Sensory Cell ◽  
Cell Regeneration ◽  
Hair Cell Regeneration ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
Technical Advances

Deafness or hearing deficits are debilitating conditions. They are often caused by loss of sensory hair cells or defects in their function. In contrast to mammals, nonmammalian vertebrates robustly regenerate hair cells after injury. Studying the molecular and cellular basis of nonmammalian vertebrate hair cell regeneration provides valuable insights into developing cures for human deafness. In this review, we discuss the current literature on hair cell regeneration in the context of other models for sensory cell regeneration, such as the retina and the olfactory epithelium. This comparison reveals commonalities with, as well as differences between, the different regenerating systems, which begin to define a cellular and molecular blueprint of regeneration. In addition, we propose how new technical advances can address outstanding questions in the field.

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