Pathology of the rat vestibular sensory epithelia during subchronic 3,3′-iminodipropionitrile exposure: hair cells may not be the primary target of toxicity

2001 ◽  
Vol 102 (4) ◽  
pp. 339-348 ◽  
Author(s):  
A. Seoane ◽  
D. Demêmes ◽  
J. Llorens
Keyword(s):  
Hair Cells ◽  
Primary Target ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia

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.

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.

scholarly journals Author response: Regenerating hair cells in vestibular sensory epithelia from humans

2018 ◽  
Author(s):  
Ruth Rebecca Taylor ◽  
Anastasia Filia ◽  
Ursula Paredes ◽  
Yukako Asai ◽  
Jeffrey R Holt ◽  
...  
Keyword(s):  
Hair Cells ◽  
Author Response ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia

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 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.

Comparative Morphology of Rodent Vestibular Periphery. I. Saccular and Utricular Maculae

2005 ◽  
Vol 93 (1) ◽  
pp. 251-266 ◽  
Author(s):  
Sapan S. Desai ◽  
Catherine Zeh ◽  
Anna Lysakowski
Keyword(s):  
Body Weight ◽  
Hair Cells ◽  
Calcium Binding ◽  
Comparative Morphology ◽  
Sensory Epithelium ◽  
Type I ◽  
Type Ii ◽  
Sensory Epithelia ◽  
Tree Squirrel ◽  
Vestibular Sensory Epithelia

Calyx afferents, a group of morphologically and physiologically distinct afferent fibers innervating the striolar region of vestibular sensory epithelia, are selectively labeled by antibodies to the calcium-binding protein calretinin. In this study, the population of calretinin-stained calyx afferents was used to delineate and quantify the striolar region in six rodent species: mouse, rat, gerbil, guinea pig, chinchilla, and tree squirrel. Morphometric studies and hair cell and calyx afferent counts were done. Numbers of hair cells, area, length, and width of the sensory epithelium increase from mouse to tree squirrel. In the mouse and rat, calretinin is found in 5–9% of all type I hair cells, 20–40% of striolar type II hair cells, and 70–80% of extrastriolar type II hair cells. Numbers of calyx afferents increase from mouse to squirrel, with more complex calyx afferents in larger species. About 10% of calyx afferents are branched. Based on our counts of total numbers of calyx afferents in chinchilla maculae and in comparison to fiber counts in the literature, the proportion of calyx afferents is greater than previously described, constituting nearly 20% of the total. Because morphometric measures increase with body weight, we obtained additional data on vestibular end organ surface areas from the literature and used this to construct a power law function describing this relationship. The function holds for species with body weights less than ∼4 kg. Greater than 4 kg, the surface area of the sensory epithelia remains constant even with increasing body weight.

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.

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