Auditory hair cells are the sensory cells that transduce sound waves into electric signals, and are located in the cochlea, the organ responsible for hearing, in the inner ear. The loss of the hair cells is the leading cause of hearing impairment. The mammalian cochlea cannot regenerate its complement of mature hair cells and therefore hearing impairment caused by hair cell loss is difficult to cure. The developmental process of cochlea, including hair cells, is complex and has not been sufficiently elucidated yet. A better understanding of it would provide clues that could lead to new strategies for hair cell regeneration. The mammalian cochlea is highly developed and hair cells are regularly arranged in rows. Research on cochlear development has shown that the cochlea is highly sensitive to disorders caused by abnormal cellular differentiation and tissue organization. This seminar will present our research on mammalian cochlear development and to discuss the approach to hair cell ...

97690 avhandlingar från svenska högskolor och universitet. Avhandling: Mechano-electrical transduction in isolated myocardium of Helix pomatia.

The hair cells of the inner ear seem to be specified properly as they express many of the typical hair cell markers such as myosin VI/VIIa, Math1 and Brn3c. Thus, Gfi1 is not required for the specification of hair cells as they are formed in both the vestibule and the cochlea. However, the loss of Gfi1 seems to affect the vestibular and cochlear hair cells differently. In the vestibule, the hair cells are morphologically abnormal at the earliest stages of hair cell differentiation and at all subsequent stages. In addition, hair cells are not specifically localized to a lumenal monolayer, and are more variable in size and shape. This disorganization of hair cells in the vestibule may account for the ataxic behavior of the mice. In the cochlea, Gfi1 is required for the organization and maintenance of both inner and outer hair cells. Although the mutant hair cells seem to be specified in the developing organ of Corti as early as E15.5 and express typical hair cell markers, they are disorganized. In ...

TY - JOUR. T1 - Regeneration of Stereocilia of Hair Cells by Forced Atoh1 Expression in the Adult Mammalian Cochlea. AU - Yang, Shi Ming. AU - Chen, Wei. AU - Guo, Wei Wei. AU - Jia, Shuping. AU - Sun, Jian He. AU - Liu, Hui Zhan. AU - Young, Wie Yen. AU - He, David Z.Z.. PY - 2012/9/27. Y1 - 2012/9/27. N2 - The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of ...

OBJECTIVE/HYPOTHESIS: Hair cells of the mammalian auditory system do not regenerate, and therefore their loss leads to irreversible hearing loss. Aminoglycosides, among other substances, can irreversibly damage hair cells. Somatostatin, a peptide with hormone/neurotransmitter properties, has neuroprotective effects by binding to its receptor. In this study, we tested whether somatostatin can protect hair cells from gentamicin-induced damage in vitro. STUDY DESIGN: This study confirmed the expression of somatostatin receptor mRNA within the cochlea and analyzed the effect of somatostatin on gentamicin-induced hair cell damage and death in vitro. METHODS: Expression of somatostatin receptor mRNA in the rat cochlea was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Protection of auditory hair cells from gentamicin was tested using two different concentrations (1 microM and 5 microM, respectively) of somatostatin. RESULTS: We detected somatostatin receptor-1 and -2 mRNA and in ...

Reactive oxygen species (ROS) play a role in the degeneration of auditory hair cells because of aging, noise trauma, or ototoxic drugs. Hydrogenation is a fundamental reduction/de-oxidation reaction in living organisms. This study thus examined the potential of hydrogen to protect auditory hair cell …

Postembryonic production of hair cells, the highly specialized receptors for hearing, balance and motion detection, occurs in a precisely controlled manner in select species, including avians. Notch1, Delta1 and Serrate1 mediate cell specification in several tissues and species. We examined expression of the chicken homologs of these genes in the normal and drug-damaged chick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent. By 3 days after drug-induced hair cell injury, Delta1 expression is highly upregulated in areas of cell proliferation in both the utricle and basilar papilla. Delta1 mRNA levels are elevated in progenitor cells during DNA synthesis and/or gap 2 phases of the cell cycle and expression ...

Death of sensory hair cells in the inner ear results in two global health problems that millions of people around the world suffer: hearing loss and balance disorders. Hair cells convert sound vibrations and head movements into electrical signals that are conveyed to the brain, and as a result of aging, exposure to noise, modern drugs or genetic predisposition, hair cells die. In mammals, the great majority of hair cells are produced during embryogenesis, and hair cells that are lost after birth are not replaceable. However, in the last decades, researches have shown some model organisms that retain the ability to regenerate hair cells damaged after embryogenesis, such as Zebrafish and chicken, providing clues as to the cellular and molecular mechanisms that may block hair cell regeneration in mammals. This discovery initiated a search for methods to stimulate regeneration or replacement of hair cells in mammals, a search that, if fruitful, will revolutionize the treatment of hearing loss and ...

In fish, amphibians, and birds, regeneration of sensory hair cells through asymmetric cell divisions of supporting cells can contribute to recovery of hearing and balance after hair cell loss caused by trauma or toxicity (1, 2). Mammalian hair cells do not spontaneously regenerate, even though supporting cells in vestibular sensory epithelia retain a limited ability to divide (3, 4). Consequently, hair cell death in mammals often leads to permanent impairment of hearing and balance.. As the inner ear develops, hair cell progenitor cells exit from the cell cycle and, like neurons, terminally differentiate. Negative cell cycle regulators apparently maintain the postmitotic status of hair cells and contribute to their terminal differentiation. The cyclin-dependent kinase inhibitors p27Kip1 and p19Ink4d participate in cell cycle exit of hair cell progenitors and in hair cell apoptosis, respectively (5, 6). However, the key regulators of cell cycle exit and concomitant hair cell terminal ...

Mature mammals exhibit very limited capacity for regeneration of auditory hair cells, while all non-mammalian vertebrates examined can regenerate them. In an effort to find therapeutic targets for deafness and balance disorders, scientists have examined gene expression patterns in auditory tissues under different developmental and experimental conditions. Microarray technology has allowed the large-scale study of gene expression profiles (transcriptomics) at whole-genome levels, but since mRNA expression does not necessarily correlate with protein expression, other methods, such as microRNA analysis and proteomics, are needed to better understand the process of hair cell regeneration. These technologies and some of the results of them are discussed in this review. Although there is a considerable amount of variability found between studies owing to different species, tissues and treatments, there is some concordance between cellular pathways important for hair cell regeneration. Since gene expression

A scientific study from the Stowers Institute of Medical Research is issued in the Journal Developmental Cell. It focuses on the regeneration of hair cells in fish and reveals an important component of this secret weapon in fish. According to the study, the support cells cause the regeneration of the sensory hair cells in fish.. The inner ear sensory hair cells succumb to age or injuries. The older an individual gets, the less likely is he to hear well. Interestingly, humans are one-upped by fish here. Fishes have hair cells in their sensory system that dots their bodies and forms the lateral line. They discern the movement of water with these cells. These cells are readily regenerated, by support cells, if damaged or death occurs. These support cells surround centrally-located hair cells in each garlic-shaped sensory organ or neuromast.. Intriguingly, mammals also have supports cells. However, they dont respond to hair cell death in a similar manner. In order to develop an insight into how ...

Hair cells, the sensory receptors of the auditory, vestibular, and lateral-line organs, may be damaged by a number of agents including aminoglycoside antibiotics and severe overstimulation. In the avian cochlea, lost hair cells can be replaced by regeneration. These new hair cells appear to be derived from a support cell precursor which is stimulated to divide by events associated with hair cell loss. Little is known about the timing and sequencing of events leading to new hair cell production. In this study cell cycle-associated events in the avian cochlea were analyzed at early and late time intervals following a single high dose of gentamicin. This single dose protocol has been shown to consistently result in extensive morphological damage and hair cell loss in the proximal region of the cochlea while sparing a morphologically undamaged distal cochlear region. This allowed for the differential analysis of the underlying support cell populations with respect to local hair cell loss. Three cell ...

in Ear, Nose, & Throat Journal (1998), 77(4), 276280282-5. Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led ... [more ▼]. Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led to new and exciting possibilities in inner ear medicine and surgery; specifically, the treatment or prevention of a variety of types of hearing losses in the foreseeable future. Sensorineural hearing loss in humans is commonly associated with a loss of auditory hair cells. It has been generally accepted that hearing loss resulting from hair cell damage is irreversible because the human ear has been considered to be incapable of regenerating or repairing these sensory elements following severe injury. An organ of Corti ...

Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell

Cochlear hair cells are mechanoreceptors of the auditory system and cannot spontaneously regenerate in adult mammals; thus hearing loss due to hair cell damage is permanent. In contrast, hair cells...

In my PhD (Bristol University, 1983) I used ion-sensitive microelectrodes to investigate pH regulation in snail neurones, supervised by Dr RC Thomas. I was awarded a Royal Society Exchange Fellowship to work in Paris (ENS), mainly with Dr Alain Marty on the muscarinic response in rat lacrimal glands, but also did some single channel work and a characterisation of a novel calcium-activated chloride current. I then switched direction towards hearing and the cochlea, doing a postdoc in Denver (UCHSC) with Dr Paul Fuchs following a short period in Bristol. We investigated the electrical resonance mechanism in chick cochlear hair cells. I next investigated the hair cell transduction mechanism in turtles, working with Andrew Crawford and Robert Fettiplace in Cambridge. In 1990 I became a temporary lecturer in Physiology, Bristol, and two years later was awarded a Wellcome Trust postdoctoral fellowship to investigate the mechanism of efferent inhibition in cochlear outer hair cells. This has been my ...

Inner-ear hair cell differentiation requires Atoh1 function, while Eya1, Six1, and Sox2 are coexpressed in sensory progenitors and mutations in these genes cause sensorineural hearing loss. However, how these genes are linked functionally and the transcriptional networks controlling hair cell induct …

Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p = 0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the

Clarin-1, a tetraspan-like membrane protein defective in Usher syndrome type IIIA (USH3A), is essential for hair bundle morphogenesis in auditory hair cells. We report a new synaptic role for clarin-1 in mouse auditory hair cells elucidated by characterization of Clrn1 total (Clrn1ex4-/-) and postnatal hair cell-specific conditional (Clrn1ex4fl/fl Myo15-Cre+/-) knockout mice. Clrn1ex4-/- mice were profoundly deaf, whereas Clrn1ex4fl/fl Myo15-Cre+/- mice displayed progressive increases in hearing thresholds, with, initially, normal otoacoustic emissions and hair bundle morphology. Inner hair cell (IHC) patch-clamp recordings for the 2 mutant mice revealed defective exocytosis and a disorganization of synaptic F-actin and CaV1.3 Ca2+ channels, indicative of a synaptopathy. Postsynaptic defects were also observed, with an abnormally broad distribution of AMPA receptors associated with a loss of afferent dendrites and defective electrically evoked auditory brainstem responses. Protein-protein ...

Cochlear Hair Cells are tuned to respond to different sound frequencies. These cells are arrayed in a tonotopic gradient, with low frequency responders at the apical end of the cochlea and high frequency responders at the basal end. Birds and reptiles uses alternative splicing of BK Channel as one facet of tuning these hair cells to transduce different sound frequencies. Isolation of cochlear cell mRNA has revealed that each cell expresses a different subset of BK Channel mRNA. BK channels (aka Slo channels) are tuned via alternative splicing of α subunit exons, thereby controlling regulatory properties, conductance and voltage sensitivity of the channel. BK Channels are present in muscle tissue and in the cochlea.. ...

The avian basilar papilla is composed of hair and supporting cells arranged in a regular pattern in which the hair cells are surrounded and isolated from each other by supporting cell processes. This arrangement of cells, in which the apical borders of hair cells do not contact one another, may be generated by contact-mediated lateral inhibition. Little is known, however, about the way in which hair and supporting cells are organized during development. Whole mounts double-labeled with antibodies to the 275 kDa hair-cell antigen and the tight junction protein cingulin were therefore used to examine the development of cell patterns in the basilar papilla. Hair cells that contact each other at their apical borders are seen during early development, especially on embryonic days (E) 8 and 9, but are no longer observed after E12. Hair and supporting cell patterns were analyzed in three different areas of the papilla at E9 and E12. In two of these regions between E9 and E12, the ratio of supporting ...

OBJECTIVES/HYPOTHESIS: The hair cells are the most vulnerable elements in the cochlea, and damage to them is the most common cause of sensorineural hearing loss. Understanding the intracellular events that lead to the death of hair cells is a key to developing protective strategies. The Fas death receptor-mediated apoptotic pathway is well studied and plays an important role in the elimination of damaged cells in a number of different cellular systems. We have studied the role of the Fas receptor in aminoglycoside-mediated toxicity in vitro. We employed the MRL/MpJ-Fas mouse, which does not express a functional Fas receptor. STUDY DESIGN: Response of Fas-deficient hair cells to gentamicin was compared with the response of normal hair cells in vitro. METHODS: Basal turn organ of Corti explants from p3-5 mice were maintained in tissue culture and treated with gentamicin for 72 hours. The explants were fixed and were stained with phalloidin, and counting was performed. RESULTS: There was no ...

Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury-induced hair cell loss, but with unsolved mechanisms. We have characterized the c-Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells and in the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by non-traumatic noise levels and as none of the cells showing this activation were lost, c-Jun phosphorylation is a biomarker for cochlear stress rather than an indicator of a death-prone fate of hair cells. Preconditioning with a mild noise exposure before a stronger traumatizing noise exposure attenuated the cochlear c-Jun stress ...

Introduction and Objective]: The cochleogram is a graphic record which represents hair cells along the length of the basilar membrane and relates cell damage with frequency specific values in hearing thresholds. The purpose of this study is to design a simple and robust method to quantitatively determine the distribution of the inner and outer hair cells at the organ of Corti in the mouse cochlea. [Materials and Methods]: Six male CBA/CaOlaHsd mice with normal auditory brainstem responses were sacrificed at 2months of age. The cochleae from both ears (n=12) were extracted, fixed and decalcified, and then divided in two parts (apical-middle and basal), obtaining around 80% of the whole extent of the basilar membrane. The organ of Corti (OC) was isolated and phalloidin-stained in multiwall glass slides. Using a fluorescence microscope and stereological software, the total length of the OC was divided into equidistant 5% sectors1. The number of inner (IHC) and outer (OHC) hair cells in randomly ...

Research on the regrowth of cochlear cells may lead to medical treatments that restore hearing. Unlike birds and fish, humans and other mammals are generally incapable of regrowing the cells of the inner ear that convert sound into neural signals when those cells are damaged by age or disease.[4][20] Researchers are making progress in gene therapy and stem-cell therapy that may allow the damaged cells to be regenerated. Because hair cells of auditory and vestibular systems in birds and fish have been found to regenerate, their ability has been studied at length.[4][21] In addition, lateral line hair cells, which have a mechanotransduction function, have been shown to regrow in organisms, such as the zebrafish.[22]. Researchers have identified a mammalian gene that normally acts as a molecular switch to block the regrowth of cochlear hair cells in adults.[23] The Rb1 gene encodes the retinoblastoma protein, which is a tumor suppressor. Rb stops cells from dividing by encouraging their exit from ...

PLoS Biol. 2013;11(6):e1001583. doi: 10.1371/journal.pbio.1001583. Epub 2013 Jun 11. Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural

The peripheral auditory system communicates with the central nervous system through synapses between the sensory cells and the spiral ganglion neurons. This sin...

The DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) causes genomic demethylation to regulate gene expression. However, it remains unclear whether 5-aza affects gene expression and cell fate determination of stem cells. In this study, 5-aza was applied to mouse utricle sensory epithelia-derived progenitor cells (MUCs) to investigate whether 5-aza stimulated MUCs to become sensory hair cells. After treatment, MUCs increased expression of hair cell genes and proteins. The DNA methylation level (indicated by percentage of 5-methylcytosine) showed a 28.57% decrease after treatment, which causes significantly repressed DNMT1 protein expression and DNMT activity. Additionally, FM1-43 permeation assays indicated that the permeability of 5-aza-treated MUCs was similar to that of sensory hair cells, which may result from mechanotransduction channels. This study not only demonstrates a possible epigenetic approach to induce tissue specific stem/progenitor cells to become sensory hair cell-like cells,

Tiny hair cells in the inner ear play an outsized role.For balance, five separate patches of hair cells sense movement and tell the brain where the head is in space while translating the pull of gravity.For hearing, a five cell-wide ribbon of 16,000 hair cells spirals inside the cochlea, the snail-shaped structure where hair cells vibrate in response to sound waves. Every cycle of sound waves sends microscopic cilia on the tips of these cells back and forth, riding a trampoline of cells suspended between two fluid-filled spaces.

Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment o

Looking for hair cell? Find out information about hair cell. The basic sensory unit of the inner ear of vertebrates; a columnar, polarized structure with specialized cilia on the free surface Explanation of hair cell

Spiral ganglion cells (SGCs, the secondary sensory neurons making up the auditory nerve) are continuously firing cells in a healthy ear (they fall silent when the hair cells degenerate, leading to deafness). In fact, their base frequency in silence is pretty high. The only thing the hair cell input does is lowering, or elevating the threshold and hence affecting firing rate. During a sine wave stimulus (a pure tone), the stereocilia of the hair cells deflect in one phase, and inflect on the other. One phase hence depolarizes the SGC, the other hyperpolarizes it. This generates a near-perfect representation of the sine wave input at low frequencies. At high frequencies the SGCs may skip a phase or two, but because multiple SGCs are involved, the population code is still stochastically spot on.. Sound level is coded in spike rate, frequency is coded by a place-frequency map (Müller, 1996). The base of the cochlea codes high frequencies, the apex low frequencies. Hence, loudness is coded by every ...

The inner ear contains the auditory and vestibular organs, which are sensory neuroepithelia composed of mechanosensory hair cells and glia-like supporting cells. The mammalian auditory sensory epithelium, the organ of Corti, is responsible for transduction of sound stimuli into electrical signals for hearing function. Hair ...

In mammals, an example of planar cell polarity (PCP) is the uniform orientation of the hair cell stereociliary bundles within the cochlea. The PCP pathway of Drosophila1,2,3,4 refers to a conserved signalling pathway that regulates the coordinated orientation of cells or structures within the plane of an epithelium. Here we show that a mutation in Vangl2, a mammalian homologue of the Drosophila PCP gene Strabismus/Van Gogh, results in significant disruptions in the polarization of stereociliary bundles in mouse cochlea as a result of defects in the direction of movement and/or anchoring of the kinocilium within each hair cell. Similar, but less severe, defects are observed in animals containing a mutation in the LAP protein family gene Scrb1 (homologous with Drosophila scribble). Polarization defects in animals heterozygous for Vangl2 and Scrb1 are comparable with Vangl2 homozygotes, demonstrating genetic interactions between these genes in the regulation of PCP in mammals. These results demonstrate a

A study of data collected from 2001-2004 estimated 35.4% of adults aged 40 and older have balance problems, with odds of dysfunction increasing significantly wi...

Foley, Shawn W., Gosai, Sager J., Wang, Dongxue, Selamoglu, Nur, Sollitti, Amelia C., Köster, Tino, Steffen, Alexander, Lyons, Eric, Daldal, Fevzi, Garcia, Benjamin A., Staiger, Dorothee, Deal, Roger B., and Gregory, Brian D. A Global View of RNA-Protein Interactions Identifies Post-transcriptional Regulators of Root Hair Cell Fate. Developmental Cell 41.2 (2017): 204-220.e5 ...

This observation in mice suggests that a person who lacks one or both copies of Ink4d, or who has Ink4d genes that are not very active, might suffer progressive hair cell death and experience hearing loss, just as mice do, according to Neil Segil, Ph.D., a researcher at the House Ear Institute and a research associate professor at the University of Southern California Medical School (Los Angeles). Segil, a senior author of a paper reporting these results, published in the May 2003 issue of Nature Cell Biology, speculates that the lack of one or both Ink4d genes makes the person more susceptible to hair cell loss from a variety of different traumas, such as loud noise or certain medicines. According to this theory, trauma could stimulate hair cells to attempt to divide, and in turn, lead to apoptosis. This suggests that a person with a full set of Ink4d genes might be less susceptible to loud noise than a person with only half the set ...

st_jude_childrens_research_hospital_investigators_have_found_that_an_electrically_powered_amplification_mechanism_in_the_cochlea_of_the_ear_is_critical_to_the_acute_hearing_of_humans_and_other_mammals_the_findings_will_enable_better_understanding_of_how_hearing_loss_can_result_from_malfunction_of_this_amplification_machinery_due_to_genetic_mutation_or_overdose_of_drugs_such_as_aspirin

hair cell definition: A cell inside organ of Corti having good hairlike processes.; a sensory epithelial cellular contained in the organ of Corti

Free Online Library: Generation of hair cells: a monumental breakthrough.( , Editorial) by Ear, Nose and Throat Journal; Health, general Hearing loss Care and treatment Causes of

Using powerful electron microscopy techniques, Gleason and her colleagues confirmed previous findings in mice studies that showed abnormalities in the hair cells. The deaf zebra fish had fewer and shorter kinocilia as well as a reduced number of stereocillia. But the researchers also found that the tips of the stereocilia were much thinner than normal stereocilia and lacked a tethering protein that connects one stereocilium to the next. The findings, says Gleason, suggest that Tmie plays a bigger role in the transmission of sound than previously thought. At the ultra-structural level, we specifically show that these mutant defects map to a very specific cog in the transduction machinery, says Gleason. And thats exciting because we now have a clearer target for therapy. ...

Katie Kindt, Ph.D., Acting Chief Research Statement The section on Sensory Cell Development and Function investigates how discrete subcellular signals, such as Ca2+ influx and vesicle release, shape hair cell development, and how these signals are required for proper physiological function.

Keywords: Vestibular, type II locks cell, morphology, mammal, synapse, JAX:000654, JAX:000664, RGD: 737903, Abdominal_10013626, Abdominal_10015251, Abdominal_2282417, Abdominal_2068506, Abdominal_2068336, Abdominal_477329, Abdominal_177520, Abdominal_10175616, Abdominal_2113875, Abdominal_399431, Abdominal_2079751, Abdominal_2286684 Intro In mammals, five vestibular body organs INO-1001 in the internal hearing encode motions of the mind and therefore regulate look, body motions, and body alignment. The saccule and utricle possess a toned physical epithelium known as a macula, and they respond to linear mind speeding and mind tilt. The anterior, posterior, and horizontal ampullae possess a even more complexly formed physical epithelium known as a crista, and they identify mind rotation in a range of aeroplanes. Locks cells are the physical mechanoreceptors in these body organs. Directional deflections of lengthy microvilli (stereocilia) on the areas of locks cells travel actions possibilities in ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transmembrane protein that is necesssary for mechanotransduction in cochlear hair cells of the inner ear. Mutations in this gene may underlie hereditary disorders of balance and hearing. [provided by RefSeq, Aug 2015 ...

Video created by 芝加哥大学 for the course 了解大脑：日常生活中的神经生物学. The vestibular system and gaze control give us so much but are grossly under appreciated. They are so fundamental that we discount them, assuming that they will always be there. When the ...

Video created by 芝加哥大学 for the course 了解大脑：日常生活中的神经生物学. The vestibular system and gaze control give us so much but are grossly under appreciated. They are so fundamental that we discount them, assuming that they will always be there. When the ...

Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin include nephrotoxicity and ototoxicity. Cisplatins ototoxic effect results in part from damage to and death of cochlear hair cells. Mechanisms underlying cisplatin-induced hair cell death are poorly understood and have been attributed to DNA damage, oxidative stress, and inflammation. This study was designed to determine the role of p53 in cisplatin-induced hair cell death and to investigate heat shock proteins (HSPs) as potential protectants against cisplatin-induced hair cell death using adult mouse utricle as an in vitro model of mature mammalian hair cells. p53 is a well-known transcription factor involved in the DNA damage response. Using p53-1 - mice and wild-type litter mates, results indicate that p53 is not necessary for cisplatin-induced death of hair cells and hearing loss. Heat shock has been previously shown to ...

Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without

TY - JOUR. T1 - Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio). AU - Uribe, Phillip M.. AU - Sun, Huifang. AU - Wang, Kevin. AU - Asuncion, James D.. AU - Wang, Qi. AU - Chen, Chien Wei. AU - Steyger, Peter S.. AU - Smith, Michael E.. AU - Matsui, Jonathan I.. PY - 2013/3/22. Y1 - 2013/3/22. N2 - Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in a variety of species including chickens, mice, and humans. The zebrafish (Danio rerio) has been used to study hair cell cytotoxicity in the lateral line organs of larval and adult animals. Little is known about whether aminoglycosides kill the hair cells within the inner ear of adult zebrafish. We report here the ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing organ, and utricle of zebrafish. First, adult zebrafish received a single 30 mg/kg intraperitoneal injection of fluorescently-tagged gentamicin (GTTR) to ...

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with ...

The goal of Ruben Stepanyans lab The goal of the labs research is to study hair cell mechanosensitivity and calcium homeostasis in normal and pathological conditions. Mechanosensitivity of hair cells is necessary for our hearing while calcium is an essential modulator of mechano-electrical transduction. During excessively loud sounds and noise a substantial amount of calcium ions enter hair cells through mechanotransduction channels. Therefore it is important for hair cells to be able to buffer and extrude excessive Ca2; compromised calcium balance is a significant factor leading to hair cell death. Outer hair cells, one of the two types of auditory hair cell in mammalian cochlea, rely on mobile calcium buffers and plasma membrane calcium pumps to regulate calcium levels. A particular interest of the lab is establishing the exact mechanism by which sounds and noise lead to calcium overload in basal, high frequency, outer hair cells. Generally, hearing loss occurs at the higher frequencies ...

During this work we investigated organization, molecular composition and function of hair cell ribbon synapses. We demonstrated RIBEYE, Bassoon and Piccolo to be components of IHC synaptic ribbons. In the present study we showed that anchoring of IHC ribbons is impaired in mouse mutants for the presynaptic scaffolding protein Bassoon. The lack of active, zone-anchored synaptic ribbons reduced the presynaptic readily releasable vesicle pool, and impaired synchronous auditory signalling as revealed by recordings of exocytic IHC capacitance changes and sound-evoked activation of spiral ganglion neurons. Both exocytosis of the hair cell releasable vesicle pool and the number of synchronously activated spiral ganglion neurons co-varied with the number of anchored ribbons during development. Interestingly, ribbon-deficient IHCs were still capable of sustained exocytosis with normal Ca2+-dependence. Endocytic membrane retrieval was intact, but an accumulation of tubular and cisternal membrane profiles ...

The site of transduction is in the organ of Corti (spiral organ). It is composed of hair cells held in place above the basilar membrane like flowers projecting up from soil, with their exposed short, hair-like stereocilia contacting or embedded in the tectorial membrane above them. The inner hair cells are the primary auditory receptors and exist in a single row, numbering approximately 3,500. The stereocilia from inner hair cells extend into small dimples on the tectorial membranes lower surface. The outer hair cells are arranged in three or four rows. They number approximately 12,000, and they function to fine tune incoming sound waves. The longer stereocilia that project from the outer hair cells actually attach to the tectorial membrane. All of the stereocilia are mechanoreceptors, and when bent by vibrations they respond by opening a gated ion channel (refer to Figure 17.2). As a result, the hair cell membrane is depolarized, and a signal is transmitted to the chochlear nerve. Intensity ...

Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFβ, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27KIP and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this

The sensory epithelia of the inner ear are composed of mechanosensory hair cells and supporting cells, organised into a checkerboard-like pattern. Hair cells are essential for hearing and their loss after exposure to excessive noise (watch your iPods!) and during ageing is the main cause of deafness in humans. This is because in the mammalian auditory organ, the full complement of hair cells is produced during embryonic development. In contrast, reptiles, fish and birds can regenerate their hair cells throughout adult life. In these species, the supporting cells act as tissue stem cells following hair cell loss. Supporting cells can i) re-enter the cell cycle to produce new hair cells and supporting cells, or ii) convert directly into replacement hair cells. What are the molecular signals and genetic networks controlling hair cell formation and regeneration? And could these be manipulated to promote regenerative processes in the mammalian ear? Research in my lab aims to provide some answers ...

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, ...

A modifier variant can abrogate risk of a monogenic disorder. DFNM1 is a locus on chromosome 1 encoding a dominant suppressor of human DFNB26 recessive, profound deafness. Here, we report that DFNB26 is associated with a substitution (p.Gly116Glu) in the pleckstrin-homology-domain of GAB1, an essential scaffold in the MET/HGF pathway. A dominant substitution (p.Arg544Gln) of METTL13, encoding a predicted methyltransferase, is the DFNM1 suppressor of GAB1-associated deafness. In zebrafish, human METTL13 mRNA harboring the modifier allele rescues the GAB1 associated morphant phenotype. In mouse, GAB1 and METTL13 co-localize in auditory sensory neurons, and METTL13 co-immunoprecipitates with GAB1 and SPRY2, indicating at least a tripartite complex. Expression of MET-signaling genes in human lymphoblastoid cells of individuals homozygous for p.Gly116Glu GAB1 revealed dysregulation of HGF, MET, SHP2, and SPRY2, all of which have reported variants associated with deafness. However, SPRY2 was not ...

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, ...

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, ...

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, ...

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, ...

BACKGROUND Cisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss.METHODS We examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).RESULTS Among patients on concurrent atorvastatin, 9.7% experienced a CTCAE grade 2 or higher cisplatin-induced hearing loss compared with 29.4% in nonstatin users (P , 0.0001). A mixed-effect model analysis showed that atorvastatin use was significantly ...

By Eshaan Soman. Abstract. Sensorineural hearing loss is a serious impairment that deprives more than 360 million people worldwide from one of their vital senses. Furthermore, more than 1.1 billion people are becoming increasingly susceptible to the condition as well (Deafness and Hearing Loss). Though common, this medical disability has no cure yet. However, gene therapy is an emerging treatment that is being developed to tackle the root causes of this morbidity.. Introduction. Humans interpret sound primarily through the auditory hair cells located in a portion of the inner ear known as the cochlea. Auditory hair cells are not actual hair cells, but have been labelled as such because they sport microscopic hair-like projections known as stereocilia at the top of each cell (Pujol). As sound waves reach the inner ear, they cause the stereocilia to sway back and forth, opening up pore-like channels at the tips of the projections. This allows chemicals to rush into the cell, converting sound ...

Terkko Navigator is a medical library community for the University of Helsinki and Helsinki University Central Hospital. Personalize your own library of feeds, journals, books, links and more ⇒ ⇒

When the stapes, a small bone that is part of the middle ear, is stimulated to remove from the oval window, a K+ rich fluid called endolymph rushes into the cochlea. This change in fluid amount causes a bend in the basilar membrane, which in turn, bends the reticular lamina, rods of Corti, and the tectorial membrane. This bending also causes the stereocilia to bend back and forth on the hair cells. On the tip of each stereocilia is a channel called transient receptor potential A1 channels or TRPA1, which allows for the inflow of K+ into the hair cell. Each TRPA1 channel is connected to one other by a link known as the tip link. This link can be thought of as a string that opens and closes a door. As the stereocilia bend each way, the doors to the channels open allowing K+ into the hair cell or close preventing K+ overflow. When K+ enters the hair cell, depolarization occurs. This unique physiological property is due to the extremely high concentration of K+ in the endolymph which results in a ...

When the stapes, a small bone that is part of the middle ear, is stimulated to remove from the oval window, a K+ rich fluid called endolymph rushes into the cochlea. This change in fluid amount causes a bend in the basilar membrane, which in turn, bends the reticular lamina, rods of Corti, and the tectorial membrane. This bending also causes the stereocilia to bend back and forth on the hair cells. On the tip of each stereocilia is a channel called transient receptor potential A1 channels or TRPA1, which allows for the inflow of K+ into the hair cell. Each TRPA1 channel is connected to one other by a link known as the tip link. This link can be thought of as a string that opens and closes a door. As the stereocilia bend each way, the doors to the channels open allowing K+ into the hair cell or close preventing K+ overflow. When K+ enters the hair cell, depolarization occurs. This unique physiological property is due to the extremely high concentration of K+ in the endolymph which results in a ...

Discovery may accelerate advances in understanding and treating hearing loss. National Institutes of Health-funded researchers have identified two proteins that may be the key components of the long-sought after mechanotransduction channel in the inner ear-the place where the mechanical stimulation of sound waves is transformed into electrical signals that the brain recognizes as sound. The findings are published in the Nov. 21 online issue of The Journal of Clinical Investigation.. The study used mice in which two genes, TMC1 and TMC2, have been deleted. The researchers revealed a specific functional deficit in the mechanotransduction channels of the mices stereocilia (bristly projections that perch atop the sensory cells of the inner ear, called hair cells), while the rest of the hair cells structure and function was normal.. These genes and the proteins they regulate are the strongest candidates yet in a decades-long search for the transduction channel that is at the center of the inner ...

This image from the lab of Patricia White, Assistant Professor of Neurobiology and Anatomy, shows a cross section of a young mouses cochlea -- the fluid-filled, inner ear structure that contains the receptor organ for hearing. Sensory hair cells are shown in pink and supporting cells in green. The sensory hair cells translate the fluid vibration of sounds into electrical impulses that are carried to the brain by sensory nerves. Age-related and noise-induced loss of hair cells in the cochlea of our inner ear is a major cause of hearing loss. So why cant mammals replace these cells as other vertebrates do? Why do surrounding supporting cells simply expand to create a scar that is insensitive to sound vibrations? Whites lab is investigating those questions, especially in light of the fact that purified immature mammalian supporting cells can divide and differentiate into new sensory hair cells under certain conditions in culture. Moreover, even mature mammalian supporting cells can differentiate ...

Alpha-tectorin is a protein that in humans is encoded by the TECTA gene. The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. GRCh38: Ensembl release 89: ENSG00000109927 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000037705 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Hughes DC, Legan PK, Steel KP, Richardson GP (Apr 1998). Mapping of the alpha-tectorin gene (TECTA) to mouse chromosome 9 and ...

Researchers can induce the generation of extra sensory hair cells in the cochlea. Mature sensory hair cells are red, while immature hair cells are green. The arrows indicate locations where hair cells are usually not found.

Animal tissues comprise multiple cell types, which are arranged in complex, elaborate patterns. One such pattern is the checkerboard-like cell arrangement, which is observed in certain tissues such as the oviduct and the auditory epithelia (1, 2). The organ of Corti in the inner ear consists of mechanosensory hair cells (subgrouped into inner and outer hair cells), which are interdigitated with various types of supporting cells (2); these cells are arranged in a checkerboard-like pattern (fig. S1). A number of genes or molecules, including those known to regulate planar cell polarity, have been implicated in the generation of the highly ordered structures in the cochlea (3-7). A mathematical model predicted that the checkerboard-like pattern could be generated by a mixture of two cell types, when their heterotypic cell-cell adhesions dominated over their homotypic ones (8). However, how the checkerboard-like pattern of cells is established is unclear.. Epithelial cell-cell adhesions are mediated ...

Definition of cochlear hair cells. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.

Gene Therapy and its Potential to Cure Deafness Losing a vital sense makes living life more difficult. Gene therapy, the process of replacing faulty genes with genes genetically engineered to replace them, can potentially cure deafness. Yashimo Raphael experimented with intentionally deafened guinea pigs and the gene Atoh 1, a gene said to replace lost hair cells in the inner ear. He found that hair cells grew, but were not fully functional. The slight aid in hearing the gene did give the guinea pigs almost completely disappeared after a few weeks time. Although the new hair cells did not function properly, the fact that they grew defied nature and was a successful start.Deafness affects millions of people in the United States every year. Cochlear implants and hearing aids are two methods to treat the hearing impaired, but the person has to rely on the device to hear sounds. First announced in Nature Medicine, scientists at the University of Michigan Medical School have discovered a gene that ...

The lack of certain critical microRNAs can result in deafness, according to findings published in the April 14 issue of PNAS. The molecules we identified could be used as a molecular tool delivered directly into the ears of deaf people to induce regeneration of important sensory cells that would improve hearing, one of the reporting researchers said. The molecules also could potentially help people with balance disorders related to inner ear function such as Menieres disease. Approximately 36 million Americans suffer from some form of hearing loss. In many cases, the cause is the degeneration of special sensory cells in the inner ear called hair cells. Excessive noise, certain medications, aging, and disease can damage or destroy hair cells. Because humans are unable to replace lost hair cells, hearing declines as they are lost. The researches identified specific microRNAs that are critical to the survival of hair cells. [Press release]. ...

To determine when the abnormal phenotypes of the hair bundles and the kinocilium were observed in aberrantly attached Nectin-3-/- HCs, we analysed the localisation of γ-tubulin in E16.5 mouse HCs. The maturation of the organ of Corti starts from the basal turn and proceeds to the apical turn of the cochlea; therefore, HCs in the apical turn are less mature than those in the middle turn (Lim and Anniko, 1985). In both the apical and middle turns of the Nectin-3-/- cochlea, HCs were aberrantly attached to each other and the immunofluorescence signals for Nectin-1 and afadin (Mllt4 - Mouse Genome Informatics) were concentrated at the boundary between attached HCs (Fig. 5A,B). In the apical turn of the Nectin-3+/- cochlea, the signal for γ-tubulin was observed in the centre of the apical surface of HCs, whereas it was positioned at the lateral side in the middle turn (Fig. 5C; supplementary material Fig. S4A). In the Nectin-3+/- cochlea, aberrantly attached HCs were fewer than in the Nectin-3-/- ...

Natures fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane ...

A cell wall with intercellular spaces. Start studying root hair cell diagram biology year 10 gcse. Gcse Biology Root Hair Cell Diagram Diagram Quizlet Root hair cell root cortex cells xylem leaf mesophyll cells exam tip if you are asked to identify the xylem or phloem in a diagram showing a cross section of a […]

TY - JOUR. T1 - Molecular architecture of the chick vestibular hair bundle. AU - Shin, Jung Bum. AU - Krey, Jocelyn F.. AU - Hassan, Ahmed. AU - Metlagel, Zoltan. AU - Tauscher, Andrew N.. AU - Pagana, James M.. AU - Sherman, Nicholas E.. AU - Jeffery, Erin D.. AU - Spinelli, Kateri J.. AU - Zhao, Hongyu. AU - Wilmarth, Phillip A.. AU - Choi, Dongseok. AU - David, Larry L.. AU - Auer, Manfred. AU - Barr-Gillespie, Peter G.. N1 - Funding Information: high-pressure freezing and imaging; D. Jorgens provided mentoring in high-pressure freezing. We would like to thank A. Cheng, B. Carragher and C. Potter for help with electron microscopy data collection at the National Resource for Automated Molecular Microscopy, supported by US National Institutes of Health (NIH) National Center for Research Resources grant RR017573. For technical assistance, we acknowledge A. Snyder of the Advanced Light Microscopy Core at The Jungers Center (Oregon Health & Science University), supported by shared instrumentation ...

Clarin-1, a tetraspan-like membrane protein defective in Usher syndrome type IIIA (USH3A), is essential for hair bundle morphogenesis in auditory hair cells.

Electrical tuning is a phenomenon by which certain vertebrates discriminate between different frequencies of sound. Electrical resonance results when the inherent oscillation in the membrane potential of hair cells corresponds to sound of a particular frequency. This gives rise to a resonance and amplification of signal with consequent transmitter release from these cells.. The inherent oscillation in membrane potential in a hair cell is brought about by an inward Calcium current and an outward Potassium current (calcium dependent). The systematic variation in the frequency of such an oscillation in hair cells that occurs across the tonotopic axis is brought about primarily by a variation in the kinetic properties of the Potassium current. Previously we had shown that some of this variation in kinetic properties of this current was brought about by alternative splicing of this BK potassium channel. However, a large part of this variation in kinetics cannot be explained by alternative splicing ...

OReilly, Molly, Kirkwood, Nerissa K, Kenyon, Emma J, Huckvale, Rosemary, Cantillon, Daire M, Waddell, Simon J, Ward, Simon E, Richardson, Guy P, Kros, Corne J and Derudas, Marco (2019) Design, synthesis and biological evaluation of a new series of carvedilol derivatives that protect sensory hair cells from aminoglycoside-induced damage by blocking the mechano-electrical transducer channel. Journal of Medicinal Chemistry. ISSN 0022-2623 Kenyon, Emma J, Kirkwood, Nerissa K, Kitcher, Siân R, OReilly, Molly, Derudas, Marco, Cantillon, Daire M, Goodyear, Richard J, Secker, Abigail, Baxendale, Sarah, Bulley, James C, Waddell, Simon J, Whitfield, Tanya T, Ward, Simon E, Kros, Corné J and Richardson, Guy P (2017) Identification of ion-channel modulators that protect against aminoglycoside-induced hair-cell death. Journal of Clinical Investigation Insight, 2 (24). ISSN 2379-3708 Derudas, Marco, Vanpouille, Christophe, Carta, Davide, Zicari, Sonia, Andrei, Graciela, Snoeck, Robert, Brancale, Andrea, ...

The zebrafish (Danio rerio) possesses two mechanosensory organs believed to be homologous to each other: the inner ear, which is responsible for the senses of audition and equilibrium, and the lateral line organ, which is involved in the detection of water movements. Eight zebrafish circler or auditory/vestibular mutants appear to have defects specific to sensory hair cell function. The circler genes may therefore encode components of the mechanotransduction apparatus and/or be the orthologous counterparts of the genes underlying human hereditary deafness. In this report, we show that the phenotype of the circler mutant, mariner, is due to mutations in the gene encoding Myosin VIIA, an unconventional myosin which is expressed in sensory hair cells and is responsible for various types of hearing disorder in humans, namely Usher 1B syndrome, DFNB2 and DFNA11. Our analysis of the fine structure of hair bundles in the mariner mutants suggests that a missense mutation within the C-terminal FERM ...

Wholesale USA brazilian hair bundles ☆ Find 11 USA brazilian hair bundles products from 4 USA manufacturers & suppliers at EC21 ☆ Choose quality brazilian hair bundles Manufacturers, Suppliers & Exporters in United States Now - EC21

Excellent Recommendations Which Will Boost Your Your hair Making It Glow!. Many people may have issues figuring out which head of hair cut, or style is the best for their face shape, and persona. Appearance isnt every little thing, but individuals notice. Consider this short article for several excellent good hair care ideas that will help you convey your persona to the other entire world!. Work with a locks serum to make frizzy head of hair into head of hair that shines. There are many serums which have been specifically designed for no matter what sort of your hair maybe you have. These serums will give your hair the sleekness and the entire body that you are looking for. Take a look at your local drugstore or salong to view whatever they have in stock.. For anyone with wavy hair, nix SLS (sodium lauryl sulfate) out of your hairdressing schedule, for bouncy, treatment-free of charge curls. SLS is actually a unpleasant stripping agent that robs hair of crucial fats. This produces the false ...

Sale Kinky Curly Hair Bundles Synthetic Hair Weave 3pcs/Lot 210g Ombre Hair Bundles Extensions for Women Enjoy ✓Free Shipping Worldwide! ✓Limited Time Sale ✓Easy Return.

The avian cochlea has a remarkable ability to regenerate sensory hair cells after injury, and a major goal of our research is to understand the molecular basis of this regenerative process. An ongoing study, conducted in collaboration with the Lovett lab (Dept. of Genetics), is using Next-Gen sequencing to profile the transcriptome of the chick cochlea throughout the time course of regeneration. Additional data suggest that the lack of FGF signaling in the mature mammalian ear may be one factor that limits regenerative ability in mammals. We are presently collaborating with the Orntiz lab (Dept. of Developmental Biology) to determine whether reactivating FGF signaling in the injured mouse cochlea can evoke some degree of sensory repair ...

An interesting discovery by researchers with be published in Neuroscience regarding the hair cells of the inner ear. Using a high voltage electron microscope, the researchers determined that the rootlets of the hair cells continue through the cell to the striated organelle which is believed to be responsible for the cells stability. With the striated organelle connecting the rootlets to the cell membrane, this offers the opportunity of feedback from the cell to the very detectors that detect motion. One of the researchers states the following: this suggests a new way to envision how hair cells work. Just as the brain adjusts the sensitivity of retinal cells in the eye to light, it may also modulate the sensitivity of hair cells in the inner ear to sound and head position. Feedback from the brain could be what changes the tension on the rootlets of the hair cells and their sensitivity to stimuli ...

Current Research and Scholarly Interests Our research focuses on the inner ear, from its earliest manifestation as one of the cranial placodes until it has developed into a mature and functioning organ. We are interested how the sensory epithelia of the inner ear that harbor the sensory hair cells develop, how the cells mature, and how these epithelia respond to toxic insults. The overarching goal of this research is to find was to regenerate lost sensory hair cells in mammals. ...

Hair transplantation has proven to be a popular and effective medical procedure for people looking to restore their lost hair. Thanks to technological advancements, the current hair transplant techniques are highly advanced and well equipped to provide the best-desired results by bringing back your lost hair. Currently, there are three major types of hair transplant procedures, including follicular unit extraction (FUE) surgery (also referred to as neo-grafting), scalp reduction, and follicular unit transplantation (FUT) surgery. It is imperative to note that the pros and cons of hair transplant surgery are uniquely different, depending on each particular procedure used.. Continue reading →. ...

Stem Cell Therapy provides an alternative form of treatment for Tinnitus caused by damage to or loss of auditory hair cells or damage to the auditory nerve.

Xia, Y.; Cao, X.; Xue, X.; Feng, Z.; Fan, Q.; Zheng, Y.; Feng, C.; Xu, H.; Xia, C.; Cheng, Y., 2015: Development of hair cells in inner ear is associated with expression and promoter methylation of Notch-1 in postnatal mice