scholarly journals Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory

2020 ◽  
Vol 29 (12) ◽  
pp. 2004-2021 ◽  
Author(s):  
Zongwei Chen ◽  
Shaoyuan Zhu ◽  
Kayla Kindig ◽  
Shengxuan Wang ◽  
Shih-Wei Chou ◽  
...  
Keyword(s):  
Hair Cells ◽  
Triple Mutant ◽  
Auditory Hair Cells ◽  
Water Motion ◽  
Transmembrane Channel ◽  
Sensory Epithelia ◽  
Genetic Sequences ◽  
Vestibular Sensory Epithelia ◽  
Vestibular Organs ◽  
Behavioral Assays

Abstract Perception of sound is initiated by mechanically gated ion channels at the tips of stereocilia. Mature mammalian auditory hair cells require transmembrane channel-like 1 (TMC1) for mechanotransduction, and mutations of the cognate genetic sequences result in dominant or recessive heritable deafness forms in humans and mice. In contrast, zebrafish lateral line hair cells, which detect water motion, require Tmc2a and Tmc2b. Here, we use standard and multiplex genome editing in conjunction with functional and behavioral assays to determine the reliance of zebrafish hearing and vestibular organs on Tmc proteins. Surprisingly, our approach using multiple mutant alleles demonstrates that hearing in zebrafish is not dependent on Tmc1, nor is it fully dependent on Tmc2a and Tmc2b. Hearing however is absent in triple-mutant zebrafish that lack Tmc1, Tmc2a and Tmc2b. These outcomes reveal a striking resemblance of Tmc protein reliance in the vestibular sensory epithelia of mammals to the maculae of zebrafish. Moreover, our findings disclose a logic of Tmc use where hearing depends on a complement of Tmc proteins beyond those employed to sense water motion.

scholarly journals ATP and ACh Evoked Calcium Transients in the Neonatal Mouse Cochlear and Vestibular Sensory Epithelia

2021 ◽  
Vol 15 ◽  
Author(s):  
Richard D. Rabbitt ◽  
Holly A. Holman
Keyword(s):  
Hair Cells ◽  
Calcium Release ◽  
Border Cells ◽  
Border Cell ◽  
Sensory Epithelia ◽  
Calcium Indicator ◽  
Intracellular Ca ◽  
Vestibular Sensory Epithelia ◽  
Calcium Induced Calcium Release ◽  
Vestibular Organs

Hair cells in the mammalian inner ear sensory epithelia are surrounded by supporting cells which are essential for function of cochlear and vestibular systems. In mice, support cells exhibit spontaneous intracellular Ca2+ transients in both auditory and vestibular organs during the first postnatal week before the onset of hearing. We recorded long lasting (>200 ms) Ca2+ transients in cochlear and vestibular support cells in neonatal mice using the genetic calcium indicator GCaMP5. Both cochlear and vestibular support cells exhibited spontaneous intracellular Ca2+ transients (GCaMP5 ΔF/F), in some cases propagating as waves from the apical (endolymph facing) to the basolateral surface with a speed of ∼25 μm per second, consistent with inositol trisphosphate dependent calcium induced calcium release (CICR). Acetylcholine evoked Ca2+ transients were observed in both inner border cells in the cochlea and vestibular support cells, with a larger change in GCaMP5 fluorescence in the vestibular support cells. Adenosine triphosphate evoked robust Ca2+ transients predominantly in the cochlear support cells that included Hensen’s cells, Deiters’ cells, inner hair cells, inner phalangeal cells and inner border cells. A Ca2+ event initiated in one inner border cells propagated in some instances longitudinally to neighboring inner border cells with an intercellular speed of ∼2 μm per second, and decayed after propagating along ∼3 cells. Similar intercellular propagation was not observed in the radial direction from inner border cell to inner sulcus cells, and was not observed between adjacent vestibular support cells.

On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse

2019 ◽  
Vol 128 (6_suppl) ◽  
pp. 125S-133S ◽  
Author(s):  
Terry J. Prins ◽  
Johnny J. Saldate ◽  
Gerald S. Berke ◽  
Larry F. Hoffman
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Vestibular Function ◽  
Null Mouse ◽  
Type I ◽  
Vestibular Hypofunction ◽  
Cellular Changes ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia ◽  
Cell Phenotypes

Objectives: Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications. Methods: Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice. Results: We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes). Conclusion: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.

Structure and Development of Vestibular Hair Cells in the Larval Bullfrog

1979 ◽  
Vol 88 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Cheuk W. Li ◽  
Edwin R. Lewis
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
High Frequency ◽  
Low Frequency ◽  
Type A ◽  
Cell Types ◽  
Sensory Organs ◽  
Sensory Epithelia ◽  
Sensory Structures ◽  
Vestibular Organs

Structure and development of hair cells in vestibular sensory organs of the larval bullfrog were examined with scanning electron microscopy. The larval vestibular sensory epithelia resembled those of the adult frog. Based on morphology of the ciliary tufts, seven hair cell types were identified. One of them, the type A hair cell, appears to be the morphogenetic precursor of other hair cell types. The size of the stereocilia of type A hair cells is comparable to the surrounding microvilli. The distribution of immature type A hair cells suggests that the periphery of the sensory epithelia is the principal growth zone and the site of formation of new hair cells. However, a far greater number of type A hair cells were found in high frequency sensitive sensory organs (sacculus, amphibian and basilar papillae) than low frequency sensitive vestibular sensory structures (canal cristae, utriculus and lagena). This phenomenon may suggest that the time period required for the maturation of type A hair cells to their ultimate hair cell types in the low frequency sensitive vestibular organs is shorter than in the high frequency sensory structures. It is also possible that the low frequency sensitive vestibular organs may have completed their morphogenetic development in the early larval stages, while morphogenesis of hair cells in the high frequency sensory structures continues throughout the lifetime of a bullfrog.

scholarly journals Retinoic acid degradation shapes zonal development of vestibular organs and sensitivity to transient linear accelerations

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazuya Ono ◽  
James Keller ◽  
Omar López Ramírez ◽  
Antonia González Garrido ◽  
Omid A. Zobeiri ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Sensory Epithelium ◽  
Conditional Knockout ◽  
Otolith Organ ◽  
Multiple Features ◽  
Balance Beam ◽  
Sensory Epithelia ◽  
Head Tremor ◽  
Vestibular Sensory Epithelia ◽  
Vestibular Organs

AbstractEach vestibular sensory epithelium in the inner ear is divided morphologically and physiologically into two zones, called the striola and extrastriola in otolith organ maculae, and the central and peripheral zones in semicircular canal cristae. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, formation of striolar/central zones is compromised, such that they resemble extrastriolar/peripheral zones in multiple features. Mutants have deficient vestibular evoked potential (VsEP) responses to jerk stimuli, head tremor and deficits in balance beam tests that are consistent with abnormal vestibular input, but normal vestibulo-ocular reflexes and apparently normal motor performance during swimming. Thus, degradation of RA during embryogenesis is required for formation of highly specialized regions of the vestibular sensory epithelia with specific functions in detecting head motions.

scholarly journals TMC1 is an essential component of a leak channel that modulates tonotopy and excitability of auditory hair cells in mice

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shuang Liu ◽  
Shufeng Wang ◽  
Linzhi Zou ◽  
Jie Li ◽  
Chenmeng Song ◽  
...  
Keyword(s):  
Hair Cells ◽  
Dependent Manner ◽  
Biological Processes ◽  
Action Potential Firing ◽  
Cochlear Hair Cells ◽  
Auditory Hair Cells ◽  
Leak Channel ◽  
Transmembrane Channel ◽  
Electrical Transducer ◽  
Potential Firing

Hearing sensation relies on the mechano-electrical transducer (MET) channel of cochlear hair cells, in which transmembrane channel-like 1 (TMC1) and transmembrane channel-like 2 (TMC2) have been proposed to be the pore-forming subunits in mammals. TMCs were also found to regulate biological processes other than MET in invertebrates, ranging from sensations to motor function. However, whether TMCs have a non-MET role remains elusive in mammals. Here, we report that in mouse hair cells, TMC1, but not TMC2, provides a background leak conductance, with properties distinct from those of the MET channels. By cysteine substitutions in TMC1, we characterized four amino acids that are required for the leak conductance. The leak conductance is graded in a frequency-dependent manner along the length of the cochlea and is indispensable for action potential firing. Taken together, our results show that TMC1 confers a background leak conductance in cochlear hair cells, which may be critical for the acquisition of sound-frequency and -intensity.

scholarly journals Regenerating hair cells in vestibular sensory epithelia from humans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ruth Rebecca Taylor ◽  
Anastasia Filia ◽  
Ursula Paredes ◽  
Yukako Asai ◽  
Jeffrey R Holt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Viral Vector ◽  
Explant Culture ◽  
Marker Genes ◽  
Cell Marker ◽  
Supporting Cells ◽  
Sensory Epithelia ◽  
Myosin Viia ◽  
Vestibular Sensory Epithelia

Human vestibular sensory epithelia in explant culture were incubated in gentamicin to ablate hair cells. Subsequent transduction of supporting cells with ATOH1 using an Ad-2 viral vector resulted in generation of highly significant numbers of cells expressing the hair cell marker protein myosin VIIa. Cells expressing myosin VIIa were also generated after blocking the Notch signalling pathway with TAPI-1 but less efficiently. Transcriptomic analysis following ATOH1 transduction confirmed up-regulation of 335 putative hair cell marker genes, including several downstream targets of ATOH1. Morphological analysis revealed numerous cells bearing dense clusters of microvilli at the apical surfaces which showed some hair cell-like characteristics confirming a degree of conversion of supporting cells. However, no cells bore organised hair bundles and several expected hair cell markers genes were not expressed suggesting incomplete differentiation. Nevertheless, the results show a potential to induce conversion of supporting cells in the vestibular sensory tissues of humans.

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