Featured
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Article
| Open Access
The Piezo channel is a mechano-sensitive complex component in the mammalian inner ear hair cell
The identity of hair cells’ mechanoelectrical transduction (MET) channel-complex components is unknown. Here, the authors used multiple biochemical, genetic, and functional approaches to show that mouse hair cells utilize Piezo1 and Piezo2 isoforms as part of the MET-complex component.
- Jeong Han Lee
- , Maria C. Perez-Flores
- & Ebenezer N. Yamoah
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Article
| Open Access
Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
The repertoire of mRNA isoforms in the cochlea remains unknown. Here, authors generated a full-length transcriptome atlas by ScISOr-seq, identified and studied Otof short isoform, extended our understanding of auditory function in isoform resolution.
- Huihui Liu
- , Hongchao Liu
- & Hao Wu
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Article
| Open Access
Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility
Outer hair cell electromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, the authors report the cryo-EM structures of thermostabilized prestin in the presence of various anions, providing insight into the mechanisms of mammalian cochlear amplification.
- Haon Futamata
- , Masahiro Fukuda
- & Osamu Nureki
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Article
| Open Access
Single particle cryo-EM structure of the outer hair cell motor protein prestin
Prestin, expressed in outer hair cell (OHC), belongs to the Slc26 transporter family and functions as a voltage-driven motor that drives OHC electromotility. Here, the authors report cryo-EM structure and characterization of gerbil prestin, with insights into its mechanism of action.
- Carmen Butan
- , Qiang Song
- & Joseph Santos-Sacchi
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Article
| Open Access
Inner hair cell stereocilia are embedded in the tectorial membrane
Hearing requires inner hair cell (IHC) stereocilia deflection, believed to result from hydrodynamic coupling due to the lack of contact with the tectorial membrane (TM). Here the authors show that IHC stereocilia are TM-embedded, and calcium rich structures in TM may facilitate sound transduction.
- Pierre Hakizimana
- & Anders Fridberger
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Article
| Open Access
Single-molecule force spectroscopy reveals the dynamic strength of the hair-cell tip-link connection
The conversion of auditory and vestibular stimuli into electrical signals is initiated by force transmitted to a mechanotransduction channel through the tip link. Here authors show that a single tip-link bond is more mechanically stable relative to classic cadherins, and that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains.
- Eric M. Mulhall
- , Andrew Ward
- & Wesley P. Wong
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Article
| Open Access
Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex
How the ear achieves its remarkable sensitivity is still not fully understood. In this study, the authors demonstrate that the deafness protein myosin-VIIa and its isoforms are essential for tensioning the tip link, thereby sensitizing the auditory receptor cell’s mechanotransduction process.
- Sihan Li
- , Andrew Mecca
- & Jung-Bum Shin
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Article
| Open Access
LMO7 deficiency reveals the significance of the cuticular plate for hearing function
In contrast to the extensively studied mechanosensory hair bundle, the cuticular plate is not as well understood. In this study, authors describe the discovery of a hair cell protein called LIM only protein 7, which is localized in the cuticular plate and the cell junction and may play a role in age-related deafness.
- Ting-Ting Du
- , James B. Dewey
- & Jung-Bum Shin
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Article
| Open Access
AAV2.7m8 is a powerful viral vector for inner ear gene therapy
Adeno-associated virus is used in gene therapy in mouse models of hearing loss. Here the authors compare vectors and find AAV2.7m8 can infect cells in the inner ear with high efficiency.
- Kevin Isgrig
- , Devin S. McDougald
- & Wade W. Chien
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Article
| Open Access
Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation
Mechanoelectrical transducer (MET) channels on the tips of inner hair cells are essential for transducing auditory sensory information. Here, the authors show that disrupting MET channel function also prevents the preservation of normal inner hair cell identity in adult mice.
- Laura F. Corns
- , Stuart L. Johnson
- & Walter Marcotti
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Article
| Open Access
Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea
Mechanoelectrical transduction channel (MET) current found in stereocilia of hair cells matures over the first postnatal week. Here the authors look at the contribution of transmembrane channel-like protein 1 and 2 (TMC1 and TMC2) to MET current during development of tonotopic gradients.
- Maryline Beurg
- , Runjia Cui
- & Bechara Kachar
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Article
| Open Access
Synaptically silent sensory hair cells in zebrafish are recruited after damage
Hair cells of the inner ear are mechanosensors that detect sound, and synapse onto afferent neurons. Here, the authors used calcium imaging to find that not all hair cells are synaptically engaged, but after damage these silent cells are synaptically engaged.
- Qiuxiang Zhang
- , Suna Li
- & Katie S. Kindt
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Article
| Open Access
Quantitative optical nanophysiology of Ca2+ signaling at inner hair cell active zones
Quantitatively studying components of the presynapse requires high resolution optical methods. Here the authors use confocal microscopy as well as 2D- and 3D-STED nanoscopy to quantify the number and activity of active zone Ca2+ channels in inner hair cells.
- Jakob Neef
- , Nicolai T. Urban
- & Tobias Moser
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Article
| Open Access
A molecular basis for water motion detection by the mechanosensory lateral line of zebrafish
In fish, water motion is detected by mechanosensitive hair cells located in the lateral line. Here the authors show that the molecular machinery for mechanotransduction, including transmembrane channel-like 2b (Tmc2b), varies depending on both hair cell location and hair bundle orientation.
- Shih-Wei Chou
- , Zongwei Chen
- & Brian M. McDermott Jr.
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Article
| Open Access
Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome
Mutations inGPSM2cause a rare disease characterized by deafness and brain abnormalities. Here the authors show that Gpsm2 forms a molecular complex with a heterotrimeric G-protein subunit, whirlin and a myosin motor to regulate actin dynamics in neurons and auditory hair cell stereocilia.
- Stephanie A. Mauriac
- , Yeri E. Hien
- & Mireille Montcouquiol
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Article
| Open Access
An elastic element in the protocadherin-15 tip link of the inner ear
Tip-link filaments convey force to activate hair cells, important sensory receptors. Here the authors solve a partial structure of human protocadherin-15, a tip-link component with an unusual Ca2+–free linker that bends and is predicted to confer flexibility to this filament during inner-ear mechanotransduction.
- Raul Araya-Secchi
- , Brandon L. Neel
- & Marcos Sotomayor
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Article
| Open Access
Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells
Sensory hair cells from the mammalian inner ear do not regenerate. Here, the authors induce direct hair cell formation from mouse embryonic stem cells using a three-dimensional culture system and observe differentiation of Type I and Type II vestibular hair cells and establishment of synapses with neurons.
- Xiao-Ping Liu
- , Karl R. Koehler
- & Jeffrey R. Holt
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Article
| Open Access
Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like
Stereocilia of the inner ear have graded heights that are thought to be regulated by the myosin-III family members MYO3A and MYO3B. Here the authors identify espin-1 and espin-like (ESPNL) as cargo that differentially influence the functions of both motors to regulate stereocilia length.
- Seham Ebrahim
- , Matthew R. Avenarius
- & Bechara Kachar
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Article
| Open Access
Reverse transduction measured in the living cochlea by low-coherence heterodyne interferometry
Mammalian hearing is remarkable for its sensitivity and frequency selectivity. Here, the authors show that outer hair cell-generated force, which amplifies sound-induced vibrations inside the cochlea, is responsible for these traits.
- Tianying Ren
- , Wenxuan He
- & Peter G. Barr-Gillespie
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Article
| Open Access
RFX transcription factors are essential for hearing in mice
Inner ear hair cells are non-regenerative mechanosensory cells essential for hearing. Here, with cell-type-specific expression analyses, the authors identify RFX transcription factors as central mediators of their survival during terminal differentiation and thus essential for hearing in mice.
- Ran Elkon
- , Beatrice Milon
- & Ronna Hertzano
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Article
| Open Access
Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier
The medial olivocochlear efferent reflex regulates cochlear outer hair cell-based amplification of sound energy. Here the authors show this dynamic control of hearing sensitivity is driven by sensory input from the outer hair cells and their type II spiral ganglion neuron innervation.
- Kristina E. Froud
- , Ann Chi Yan Wong
- & Gary D. Housley
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Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling
Cochlear sensory hair cells produced during development are not replaced after loss so converting the surrounding supporting cells into hair cells could be a potential regenerative strategy. Here the authors show that hair cells can be directly generated from adjacent supporting cells in developing mouse embryos by inhibition of ephrin-B2 signalling.
- Jean Defourny
- , Susana Mateo Sánchez
- & Brigitte Malgrange
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Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle
The balancing apparatus of the inner ear relies on the mechanosensory activity of hair cells (HC), which are poorly regenerated upon loss in adult mammals. Here, the authors show that in newborn mice HC regenerate through proliferation and transdifferentiation of activated striolar supporting cells that express Lgr5.
- Tian Wang
- , Renjie Chai
- & Alan G. Cheng
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A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear
The auditory systems of animals that perceive sounds in air are organized so that mechanosensory hair cells located at different positions respond to specific frequencies. Here, Mann et al. find that a gradient of Bmp7 controls the determination of frequency-specific hair cell characteristics in the chick auditory system.
- Zoë F. Mann
- , Benjamin R. Thiede
- & Matthew W. Kelley
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Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea
Precise frequency discrimination is a hallmark of auditory function in birds and mammals and relies on specific phenotypic patterning of the sensory hair cells in the inner ear. Here, Thiede et al. compare the transcriptomes of different regions of the embryonic chicken cochlea and find that retinoic acid plays a role in patterning the phenotypes of frequency-tuned hair cells in the cochlea.
- Benjamin R. Thiede
- , Zoë F. Mann
- & Jeffrey T. Corwin
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Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells
Cochlear inner and outer hair cells receive afferent innervation from type I and type II spiral ganglion neurons, respectively. Defourny et al. find that, in the absence of ephrin-A5 and its receptor EphA4, a subset of type I spiral ganglion neuron projections invade the outer hair cell area.
- Jean Defourny
- , Anne-Lise Poirrier
- & Brigitte Malgrange
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Sound-induced length changes in outer hair cell stereocilia
In the inner ear, sound waves produce movements in hair cell sterocilia, triggering the opening of ion channels. Hakizimana and colleagues show that the resultant currents change the length of sterocilia, and that these length changes alter the efficiency by which sound is converted into electrical signals.
- Pierre Hakizimana
- , William E. Brownell
- & Anders Fridberger
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The amniote paratympanic organ develops from a previously undiscovered sensory placode
The paratympanic organ in the avian middle ear is similar to the fish spiracular organ, but its developmental origin is unresolved. O'Neillet al. use fate mapping techniques to show that the avian paratympanic organ and its afferent neurons arise from a previously undiscovered neurogenic placode.
- Paul O'Neill
- , Siu-Shan Mak
- & Clare V.H. Baker
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Review Article |
Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction
Hair cells of the inner ear transduce vibrations of the basilar membrane into electrical signals by a process known as mechanotransduction. Recent advances in genetic and molecular tools have led to an improved understanding of mechanotransduction as Peng and colleagues summarize in this Review.
- Anthony W. Peng
- , Felipe T. Salles
- & Anthony J. Ricci
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Article
| Open Access
Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
Progressive sensorineural hearing loss affects many people, but the underlying genetics remain largely undefined. Here, the authors identify mutations inGIPC3in mice and two consanguineous families that lead to hearing loss and in mice cause defects in the structure of stereocilia bundles and audiogenic seizures.
- Nikoletta Charizopoulou
- , Andrea Lelli
- & Konrad Noben-Trauth
A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss