Faculty Opinions recommendation of TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear.

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

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Identification and characterization of amphibian SLC26A5 using RNA-Seq

BMC Genomics ◽

10.1186/s12864-021-07798-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhongying Wang ◽

Qixuan Wang ◽

Hao Wu ◽

Zhiwu Huang

Keyword(s):

Amino Acid ◽

Inner Ear ◽

Hair Cells ◽

Rana Catesbeiana ◽

Site Directed Mutagenesis ◽

Amino Acid Residues ◽

Rna Seq ◽

American Bullfrog ◽

Frog Species

Abstract Background Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system. Limited knowledge of prestin is from experiments using site-directed mutagenesis or domain-swapping techniques after the amino acid residues were identified by comparing the sequence of prestin to those of its paralogs and orthologs. Frog prestin is the only representative in amphibian lineage and the studies of it were quite rare with only one species identified. Results Here we report a new coding sequence of SLC26A5 for a frog species, Rana catesbeiana (the American bullfrog). In our study, the SLC26A5 gene of Rana has been mapped, sequenced and cloned successively using RNA-Seq. We measured the nonlinear capacitance (NLC) of prestin both in the hair cells of Rana’s inner ear and HEK293T cells transfected with this new coding gene. HEK293T cells expressing Rana prestin showed electrophysiological features similar to that of hair cells from its inner ear. Comparative studies of zebrafish, chick, Rana and an ancient frog species showed that chick and zebrafish prestin lacked NLC. Ancient frog’s prestin was functionally different from Rana. Conclusions We mapped and sequenced the SLC26A5 of the Rana catesbeiana from its inner ear cDNA using RNA-Seq. The Rana SLC26A5 cDNA was 2292 bp long, encoding a polypeptide of 763 amino acid residues, with 40% identity to mammals. This new coding gene could encode a functionally active protein conferring NLC to both frog HCs and the mammalian cell line. While comparing to its orthologs, the amphibian prestin has been evolutionarily changing its function and becomes more advanced than avian and teleost prestin.

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Hes1andHes5Activities Are Required for the Normal Development of the Hair Cells in the Mammalian Inner Ear

Journal of Neuroscience ◽

10.1523/jneurosci.21-13-04712.2001 ◽

2001 ◽

Vol 21 (13) ◽

pp. 4712-4720 ◽

Cited By ~ 196

Author(s):

Azel Zine ◽

Alexandre Aubert ◽

Jiping Qiu ◽

Stavros Therianos ◽

Francois Guillemot ◽

...

Keyword(s):

Inner Ear ◽

Hair Cells ◽

Normal Development

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Nonlinearities in Threshold-Level Detection by Inner Ear Hair Cells

Biophysical Journal ◽

10.1016/j.bpj.2011.11.3568 ◽

2012 ◽

Vol 102 (3) ◽

pp. 655a

Author(s):

Yuttana Roongthumskul ◽

Albert Kao ◽

Sebastiaan W.F. Meenderink ◽

Dolores Bozovic

Keyword(s):

Inner Ear ◽

Hair Cells ◽

Threshold Level

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Hes1 is a negative regulator of inner ear hair cell differentiation

Development ◽

10.1242/dev.127.21.4551 ◽

2000 ◽

Vol 127 (21) ◽

pp. 4551-4560 ◽

Cited By ~ 5

Author(s):

J.L. Zheng ◽

J. Shou ◽

F. Guillemot ◽

R. Kageyama ◽

W.Q. Gao

Keyword(s):

Cell Differentiation ◽

Hair Cell ◽

Inner Ear ◽

Cell Fate ◽

Hair Cells ◽

Outer Hair Cells ◽

Negative Regulator ◽

Pcr Analysis ◽

Loss Of Function ◽

Hair Cell Differentiation

Hair cell fate determination in the inner ear has been shown to be controlled by specific genes. Recent loss-of-function and gain-of-function experiments have demonstrated that Math1, a mouse homolog of the Drosophila gene atonal, is essential for the production of hair cells. To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis. We report here that targeted deletion of Hes1 leads to formation of supernumerary hair cells in the cochlea and utricle of the inner ear. RT-PCR analysis shows that Hes1 is expressed in inner ear during hair cell differentiation and its expression is maintained in adulthood. In situ hybridization with late embryonic inner ear tissue reveals that Hes1 is expressed in supporting cells, but not hair cells, of the vestibular sensory epithelium. In the cochlea, Hes1 is selectively expressed in the greater epithelial ridge and lesser epithelial ridge regions which are adjacent to inner and outer hair cells. Co-transfection experiments in postnatal rat explant cultures show that overexpression of Hes1 prevents hair cell differentiation induced by Math1. Therefore Hes1 can negatively regulate hair cell differentiation by antagonizing Math1. These results suggest that a balance between Math1 and negative regulators such as Hes1 is crucial for the production of an appropriate number of inner ear hair cells.

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High-Voltage Electron Microscopic Study of the Inner Ear: Technique and Preliminary Results

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894830920s101 ◽

1983 ◽

Vol 92 (1_suppl) ◽

pp. 3-12 ◽

Cited By ~ 9

Author(s):

Tomonori Takasaka ◽

Hideich Shinkawa ◽

Kozo Watanuki ◽

Sho Hashimoto ◽

Kazutomo Kawamoto

Keyword(s):

Electron Microscopy ◽

Hair Cell ◽

Inner Ear ◽

High Voltage ◽

Hair Cells ◽

Outer Hair Cells ◽

Tectorial Membrane ◽

Preliminary Results ◽

Voltage Electron ◽

Cuticular Plate

The technique and some preliminary results of the application of high-voltage electron microscopy (HVEM) to the study of inner ear morphology in the guinea pig are reported in this paper. The main advantage of HVEM is that sharp images of thicker specimens can be obtained because of the greater penetrating power of high energy electrons. The optimum thickness of the sections examined with an accelerating voltage of 1,000 kV was found to be between 500 to 800 nm. The sections below 500 nm in thickness often had insufficient contrast, while those above 800 nm were rather difficult to interpret due to overlap of images of the organelles. The whole structure of the sensory hairs from the tip to the rootlet was more frequently observed in the 800-nm thick sections. Thus the fine details of the hair attachment to the tectorial membrane as well as the hair rootlet extension into the cuticular plate could be thoroughly studied in the HVEM. In specimens fixed in aldehyde containing 2% tannic acid, the attachment of the tips of the outer hair cell stereocilia to the tectorial membrane was observed. For the inner hair cells, however, the tips of the hairs were separated from the undersurface of the tectorial membrane. The majority of the rootlets of the outer hair cells terminated at the midportion of the cuticular plate, while most of the inner hair cell rootlets traversed the entire width of the cuticular plate and extended into the apical cytoplasm. These differences in ultrastructural appearance may indicate that the two kinds of hair cells play different roles in the acoustic transduction process. The three-dimensional arrangement of the nerve endings on the hair cells was also studied by the serial thick-sectioning technique in the HVEM. In general, an entire arrangement of the nerve endings was almost completely cut in less than ten 800-nm thick sections instead of the 50- to 100-ultrathin (ie, less than 100 nm) conventional sections for transmission electron microscopy. The present study confirms an earlier report that the first row outer hair cells in the third cochlear turn are innervated by nearly equal numbers of efferent and afferent endings, the average number being nine.

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