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https://www.readbyqxmd.com/read/29769265/reciprocal-negative-regulation-between-lmx1a-and-lmo4-is-required-for-inner-ear-formation
#1
Yanhan Huang, Jennifer Hill, Andrew Yatteau, Loksum Wong, Tao Jiang, Jelena Petrovic, Lin Gan, Lijin Dong, Doris K Wu
LIM-domain containing transcription factors (LIM-TFs) are conserved factors important for embryogenesis. The specificity of these factors in transcriptional regulation is conferred by the complexes they form with other proteins such as LIM-domain-binding (Ldb) proteins and LIM-domain only (LMO) proteins. Unlike LIM-TF, these proteins do not bind DNA directly. LMO are negative regulators of LIM-TF and they function by competing with LIM-TFs for binding to Ldbs. Although the LIM-TF Lmx1a is expressed in the developing mouse hindbrain, which provides many of the extrinsic signals for inner ear formation, conditional knockout embryos of both sexes show that the inner ear source of Lmx1a is the major contributor of ear patterning...
May 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29765956/transcriptomic-profiling-of-zebrafish-hair-cells-using-ribotag
#2
Maggie S Matern, Alisha Beirl, Yoko Ogawa, Yang Song, Nikhil Paladugu, Katie S Kindt, Ronna Hertzano
The zebrafish inner ear organs and lateral line neuromasts are comprised of a variety of cell types, including mechanosensitive hair cells. Zebrafish hair cells are evolutionarily homologous to mammalian hair cells, and have been particularly useful for studying normal hair cell development and function. However, the relative scarcity of hair cells within these complex organs, as well as the difficulty of fine dissection at early developmental time points, makes hair cell-specific gene expression profiling technically challenging...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29755320/mechanically-gated-ion-channels-in-mammalian-hair-cells
#3
REVIEW
Xufeng Qiu, Ulrich Müller
Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET) channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS)/LHFPL5, transmembrane inner ear (TMIE) and transmembrane channel-like proteins 1 and 2 (TMC1/2)...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29754876/bone-morphogenetic-protein-4-antagonizes-hair-cell-regeneration-in-the-avian-auditory-epithelium
#4
Rebecca M Lewis, Jesse J Keller, Liangcai Wan, Jennifer S Stone
Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics...
May 2, 2018: Hearing Research
https://www.readbyqxmd.com/read/29740017/atoh1-rfx1-rfx3-transcription-factors-facilitate-the-differentiation-and-characterisation-of-inner-ear-hair-cell-like-cells-from-patient-specific-induced-pluripotent-stem-cells-harbouring-a8344g-mutation-of-mitochondrial-dna
#5
Yen-Chun Chen, Chia-Ling Tsai, Yau-Huei Wei, Yu-Ting Wu, Wei-Ting Hsu, Hung-Ching Lin, Yi-Chao Hsu
Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7AmCherry -positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles...
April 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29688099/no-evidence-for-enhanced-processing-of-speech-that-is-low-pass-filtered-near-the-edge-frequency-of-cochlear-dead-regions-in-children
#6
Alicja N Malicka, Wayne J Wilson, Thomas Baer, Kevin J Munro, Richard J Baker, Deanna Miluzzi, Brian C J Moore
OBJECTIVES: Cochlear dead regions (DRs) are regions in the cochlea where the inner hair cells and/or neurons are not functioning. Adults with extensive high-frequency DRs have enhanced abilities in processing sounds with frequencies just below the edge frequency, fedge , of the DR. It was assessed whether the same is true for children. DESIGN: Performance was compared for children aged 8 to 13 years with: DRs (group DR), hearing impairment but without DRs (group NODR), and normal hearing (group NH)...
April 24, 2018: International Journal of Audiology
https://www.readbyqxmd.com/read/29675997/hearing-vulnerability-after-noise-exposure-in-a-mouse-model-of-reactive-oxygen-species-overproduction
#7
Shigefumi Morioka, Hirofumi Sakaguchi, Taro Yamaguchi, Yuzuru Ninoyu, Hiroaki Mohri, Takashi Nakamura, Yasuo Hisa, Kiyokazu Ogita, Naoaki Saito, Takehiko Ueyama
Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise-induced hearing loss (NIHL), drug-induced hearing loss, and age-related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4-TG mice), which is a constitutively active ROS-producing enzyme that does not require stimulation or an activator...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29674954/bioinformatic-integration-of-molecular-networks-and-major-pathways-involved-in-mice-cochlear-and-vestibular-supporting-cells
#8
Teresa Requena, Alvaro Gallego-Martinez, Jose A Lopez-Escamez
Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29673641/a-novel-nanoparticle-delivery-system-for-targeted-therapy-of-noise-induced-hearing-loss
#9
Mohammad N Kayyali, Julian R A Wooltorton, Andrew J Ramsey, Mei Lin, Tiffany N Chao, Andrew Tsourkas, Bert W O'Malley, Daqing Li
Hearing loss is the most prevalent sensory disability worldwide and may be caused by age, drugs or exposure to excessive noise. We have previously developed a minimally-invasive nanohydrogel drug delivery system that successfully delivers nanoparticles into the inner ear. We have substantially extended this technique by functionalizing the nanoparticles and introducing a targeting peptide which recognizes prestin, a transmembrane electromotile protein uniquely expressed in outer hair cells (OHCs) of the inner ear...
April 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29662441/characterization-of-hair-cell-like-cells-converted-from-supporting-cells-after-notch-inhibition-in-cultures-of-the-organ-of-corti-from-neonatal-gerbils
#10
Yi Li, Shuping Jia, Huizhan Liu, Tomoko Tateya, Weiwei Guo, Shiming Yang, Kirk W Beisel, David Z Z He
The senses of hearing and balance depend upon hair cells, the sensory receptors of the inner ear. Hair cells transduce mechanical stimuli into electrical activity. Loss of hair cells as a result of aging or exposure to noise and ototoxic drugs is the major cause of noncongenital hearing and balance deficits. In the ear of non-mammals, lost hair cells can spontaneously be replaced by production of new hair cells from conversion of supporting cells. Although supporting cells in adult mammals have lost that capability, neonatal supporting cells are able to convert to hair cells after inhibition of Notch signaling...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29659185/the-cochlear-spiral-ganglion-neurons-the-auditory-portion-of-the-viii-nerve
#11
Francisco Carricondo, Bárbara Romero-Gómez
The VIII nerve is formed by sensory neurons that innervate the inner ear, i.e. the vestibular and the auditory receptors. Neurons of the auditory portion, the cochlear afferent fibers that innervate the sensory hair cells of the organ of Corti, have their somas in the cochlear spiral ganglion where two types of neurons can be distinguished. Afferent type-I neurons are the 95% of the total population. Bipolar and myelinated fibers, each one innervates only one cochlear inner hair cell (IHC). In contrast, afferent type-II neurons are only the 5% of the spiral ganglion population...
April 16, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29623936/cell-proliferation-during-hair-cell-regeneration-induced-by-math-1-in-vestibular-epithelia-in-vitro
#12
Yi-Bo Huang, Rui Ma, Juan-Mei Yang, Zhao Han, Ning Cong, Zhen Gao, Dongdong Ren, Jing Wang, Fang-Lu Chi
Hair cell regeneration is the fundamental method of correcting hearing loss and balance disorders caused by hair cell damage or loss. How to promote hair cell regeneration is a hot focus in current research. In mammals, cochlear hair cells cannot be regenerated and few vestibular hair cells can be renewed through spontaneous regeneration. However, Math1 gene transfer allows a few inner ear cells to be transformed into hair cells in vitro or in vivo. Hair cells can be renewed through two possible means in birds: supporting cell differentiation and transdifferentiation with or without cell division...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29618634/mice-harbouring-an-oculodentodigital-dysplasia-linked-cx43-g60s-mutation-have-severe-hearing-loss
#13
Julia M Abitbol, John J Kelly, Kevin J Barr, Brian L Allman, Dale W Laird
Given the importance of connexin43 (Cx43) function in the central nervous system and sensory organ processing we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express GJA1 (Cx43) mutations resulting in mild or severe loss of Cx43 function. Although Cx43I130T/+ mutant mice with ∼50% Cx43 channel function did not have any hearing loss, Cx43G60S/+ mutant mice with ∼20% Cx43 channel function had severe hearing loss...
April 3, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29590114/mutations-in-diphosphoinositol-pentakisphosphate-kinase-ppip5k2-are-associated-with-hearing-loss-in-human-and-mouse
#14
Rizwan Yousaf, Chunfang Gu, Zubair M Ahmed, Shaheen N Khan, Thomas B Friedman, Sheikh Riazuddin, Stephen B Shears, Saima Riazuddin
Autosomal recessive nonsyndromic hearing loss is a genetically heterogeneous disorder. Here, we report a severe-to-profound sensorineural hearing loss locus, DFNB100 on chromosome 5q13.2-q23.2. Exome enrichment followed by massive parallel sequencing revealed a c.2510G>A transition variant in PPIP5K2 that segregated with DFNB100-associated hearing loss in two large apparently unrelated Pakistani families. PPIP5Ks enzymes interconvert 5-IP7 and IP8, two key members of the inositol pyrophosphate (PP-IP) cell-signaling family...
March 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29567975/loss-of-idh2-accelerates-age-related-hearing-loss-in-male-mice
#15
Karessa White, Mi-Jung Kim, Chul Han, Hyo-Jin Park, Dalian Ding, Kevin Boyd, Logan Walker, Paul Linser, Zaimary Meneses, Cole Slade, Jonathan Hirst, Katherine Santostefano, Naohiro Terada, Takuya Miyakawa, Masaru Tanokura, Richard Salvi, Shinichi Someya
Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH. In the mitochondria, IDH2 also plays a key role in protecting mitochondrial components from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates age-related hearing loss, the most common form of hearing impairment, in male mice. This was accompanied by increased oxidative DNA damage, increased apoptotic cell death, and profound loss of spiral ganglion neurons and hair cells in the cochlea of 24-month-old Idh2-/- mice...
March 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29536272/spatiotemporal-coordination-of-cellular-differentiation-and-tissue-morphogenesis-in-organ-of-corti-development
#16
REVIEW
Akiko Iizuka-Kogo
The organ of Corti, an acoustic sensory organ, is a specifically differentiated epithelium of the cochlear duct, which is a part of the membranous labyrinth in the inner ear. Cells in the organ of Corti are generally classified into two kinds; hair cells, which transduce the mechanical stimuli of sound to the cell membrane electrical potential differences, and supporting cells. These cells emerge from homogeneous prosensory epithelium through cell fate determination and differentiation. In the organ of Corti organogenesis, cell differentiation and the rearrangement of their position proceed in parallel, resulting in a characteristic alignment of mature hair cells and supporting cells...
March 13, 2018: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29523503/the-physiological-bases-of-hidden-noise-induced-hearing-loss-protocol-for-a-functional-neuroimaging-study
#17
Rebecca Susan Dewey, Deborah A Hall, Hannah Guest, Garreth Prendergast, Christopher J Plack, Susan T Francis
BACKGROUND: Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as hidden hearing loss have been confirmed in several rodent species, but the implications for human hearing are unclear. OBJECTIVE: Our Medical Research Council-funded program aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure...
March 9, 2018: JMIR Research Protocols
https://www.readbyqxmd.com/read/29515374/trpv6-trpm6-and-trpm7-do-not-contribute-to-hair-cell-mechanotransduction
#18
Clive P Morgan, Hongyu Zhao, Meredith LeMasurier, Wei Xiong, Bifeng Pan, Piotr Kazmierczak, Matthew R Avenarius, Michael Bateschell, Ruby Larisch, Anthony J Ricci, Ulrich Müller, Peter G Barr-Gillespie
Hair cells of the inner ear transduce mechanical stimuli like sound or head movements into electrical signals, which are propagated to the central nervous system. The hair-cell mechanotransduction channel remains unidentified. We tested whether three transient receptor channel (TRP) family members, TRPV6, TRPM6 and TRPM7, were necessary for transduction. TRPV6 interacted with USH1C (harmonin), a scaffolding protein that participates in transduction. Using a cysteine-substitution knock-in mouse line and methanethiosulfonate (MTS) reagents selective for this allele, we found that inhibition of TRPV6 had no effect on transduction in mouse cochlear hair cells...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29515364/junctional-e-cadherin-p120-catenin-is-correlated-with-the-absence-of-supporting-cells-to-hair-cells-conversion-in-postnatal-mice-cochleae
#19
Wen-Wei Luo, Xin-Wei Wang, Rui Ma, Fang-Lu Chi, Ping Chen, Ning Cong, Yu-Yan Gu, Dong-Dong Ren, Juan-Mei Yang
Notch inhibition is known to generate supernumerary hair cells (HCs) at the expense of supporting cells (SCs) in the mammalian inner ear. However, inhibition of Notch activity becomes progressively less effective at inducing SC-to-HC conversion in the postnatal cochlea and balance organs as the animal ages. It has been suggested that the SC-to-HC conversion capacity is inversely correlated with E-cadherin accumulation in postnatal mammalian utricles. However, whether E-cadherin localization is linked to the SC-to-HC conversion capacity in the mammalian inner ear is poorly understood...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29513752/anti-cancer-characteristics-and-ototoxicity-of-platinum-ii-amine-complexes-with-only-one-leaving-ligand
#20
Jerry D Monroe, Heidi L Hruska, Hannah K Ruggles, Kevin M Williams, Michael E Smith
Unlike cisplatin, which forms bifunctional DNA adducts, monofunctional platinum(II) complexes bind only one strand of DNA and might target cancer without causing auditory side-effects associated with cisplatin treatment. We synthesized the monofunctional triamine-ligated platinum(II) complexes, Pt(diethylenetriamine)Cl, [Pt(dien)Cl]+, and Pt(N,N-diethyldiethylenetriamine)Cl, [Pt(Et2dien)Cl]+, and the monofunctional heterocyclic-ligated platinum(II) complexes, pyriplatin and phenanthriplatin, and compared their 5'-GMP binding rates, cellular compartmental distribution and cellular viability effects...
2018: PloS One
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