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14 results on '"MESH: Hair Cells, Auditory"'

1. Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function

Author

Aziz El-Amraoui, Stuart L. Johnson, Christine Petit, Michelle Simon, Prashanthini Jeyarajan, Lauren Chessum, Michael R. Bowl, Sherylanne Newton, Andrea Lelli, Helena Rr Wells, Frances M K Williams, Andrew Parker, Joanne Dorning, Didier Dulon, Susan Morse, Suhasini R. Gopal, Steve D.M. Brown, Sedigheh Delmaghani, Philomena Mburu, Christopher T. Esapa, Ronna Hertzano, Sara Wells, Debbie Williams, Carlos A. Aguilar, Kumar N. Alagramam, Pranav Patni, Thibault Peineau, Walter Marcotti, Laura F. Corns, Sally J. Dawson, Gemma F. Codner, Lucy A Dunbar, MRC Harwell Institute [UK], Déficits Sensoriels Progressifs, Pathophysiologie et Thérapie / Progressive Sensory Disorders, PathoPhysiology and Therapy, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Sheffield [Sheffield], King‘s College London, Génétique et Physiologie de l'Audition, Hines VA Medical Center [USA], Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Mary Lyon Centre, MRC Harwell Institute, Neurophysiologie de la Synapse Auditive, Neuroscience Institute-Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Case Medical Center (CLEVELAND - UHCMC), University Hospitals Case Medical Center, University of Maryland School of Medicine, University of Maryland System, University College of London [London] (UCL), This work was supported by: Medical Research Council (MC_U142684175 to S.D.M.B. and MC_UP_1503/2 to M.R.B), Wellcome Trust (102892 to W.M.), the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' programme (light4deaf, ANR-15-RHUS-0001) and LHW-Stiftung (to C.P. & A.E.), ANR-HearInNoise-(ANR-17-CE16-0017 to A.E.), NIDCD/NIH (R01DC013817), NIMH/NIH (R24MH114815) and the Hearing Restoration Program of the Hearing Health Foundation (to R.H.), and an Action on Hearing Loss PhD studentship (to F.W. and S.Da.), which was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. L.D. is a Medical Research Council PhD student. P.P. benefited from a fellowship from the European Union's Horizon 2020 Marie Sklodowska-Curie grant No 665807. S.L.J. is a Royal Society University Research Fellow., ANR-15-RHUS-0001,LIGHT4DEAF,ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER(2015), ANR-17-CE16-0017,HearInNoise,Surdité d'apparition tardive et progressive: de la physiopathologie à la thérapie(2017), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Collège de France - Chaire Génétique et physiologie cellulaire, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de Bordeaux Pellegrin [Bordeaux]-Neuroscience Institute, EL-AMRAOUI, Aziz, ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER - - LIGHT4DEAF2015 - ANR-15-RHUS-0001 - RHUS - VALID, Surdité d'apparition tardive et progressive: de la physiopathologie à la thérapie - - HearInNoise2017 - ANR-17-CE16-0017 - AAPG2017 - VALID, and Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID

Subjects
Male, 0301 basic medicine, Medicine (General), [SDV]Life Sciences [q-bio], QH426-470, Cohort Studies, Mice, Transduction (genetics), 0302 clinical medicine, Hearing, MESH: Hair Cells, Auditory, Molecular Biology of Disease, MESH: Animals, Mechanotransduction, MESH: Cohort Studies, MESH: Aged, Mice, Inbred C3H, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Middle Aged, stereocilia Subject Categories Genetics, Articles, Middle Aged, [SDV] Life Sciences [q-bio], Molecular Medicine, Female, medicine.symptom, MESH: Stereocilia, mutagenesis, Adult, hair cells, Hearing loss, Biology, Gene Therapy & Genetic Disease, Article, 03 medical and health sciences, R5-920, MESH: Mice, Inbred C57BL, Hair Cells, Auditory, Genetics, medicine, otorhinolaryngologic diseases, Animals, Humans, mouse models, Hearing Loss, MESH: Mice, Inbred C3H, MESH: Hearing, MESH: Hearing Loss, MESH: Mice, stereocilia, Aged, mechanotransduction, MESH: Humans, Molecular, MESH: Adult, Sensory hair, Progressive hearing loss, MESH: Male, Mice, Inbred C57BL, 030104 developmental biology, Genetics, Gene Therapy & Genetic Disease, sense organs, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genetic screen
Abstract

International audience; Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, genome mapping and gene complementation tests, we identified Clrn2 as a new deafness gene. The Clrn2 clarinet/clarinet mice (p.Trp4* mutation) exhibit a progressive, early-onset hearing loss, with no overt retinal deficits. Utilizing data from the UK Biobank study, we could show that CLRN2 is involved in human non-syndromic progressive hearing loss. Our indepth morphological, molecular and functional investigations establish that while it is not required for initial formation of cochlear sensory hair cell stereocilia bundles, clarin-2 is critical for maintaining normal bundle integrity and functioning. In the differentiating hair bundles, lack of clarin-2 leads to loss of mechano-electrical transduction, followed by selective progressive loss of the transducing stereocilia. Together, our findings demonstrate a key role for clarin-2 in mammalian hearing, providing insights into the interplay between mechano-electrical transduction and stereocilia maintenance.

Published
2019
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2. Genes Involved in the Development and Physiology of Both the Peripheral and Central Auditory Systems

Author

Nicolas Michalski, Christine Petit, Génétique et Physiologie de l'Audition, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), This work was supported by the Prix Emergence of the Agir Pour l'Audition foundation to N.M. and by grants from the French Agence Nationale pour la Recherche (ANR), as part of the second Investissements d'Avenir program (ANR-15-RHUS-0001), the LabEx Lifesenses (ANR-10-LABX-65), the European Research Council (ERC-2011-ADG_294570), the BNP Paribas Foundation, the FAUN Stiftung, and the LHW-Stiftung to C.P., ANR-15-RHUS-0001,LIGHT4DEAF,ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER(2015), ANR-10-LABX-0065,LIFESENSES,DES SENS POUR TOUTE LA VIE(2010), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), michalski, nicolas, ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER - - LIGHT4DEAF2015 - ANR-15-RHUS-0001 - RHUS - VALID, DES SENS POUR TOUTE LA VIE - - LIFESENSES2010 - ANR-10-LABX-0065 - LABX - VALID, Assembling the puzzle of the operating auditory hair bundle - HAIRBUNDLE - - EC:FP7:ERC2012-12-01 - 2017-11-30 - 294570 - VALID, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Collège de France - Chaire Génétique et physiologie cellulaire

Subjects
0301 basic medicine, MESH: Gene Ontology, Auditory Pathways, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, cochlea, Gene regulatory network, MESH: Hearing Disorders, Ion Channels, 0302 clinical medicine, MESH: Sensory Receptor Cells, MESH: Cochlea, MESH: Gene Expression Regulation, Developmental, auditory cortex, MESH: Hair Cells, Auditory, MESH: Animals, MESH: Nerve Tissue Proteins, Hearing Disorders, auditory hindbrain, General Neuroscience, Gene Expression Regulation, Developmental, MESH: Rhombencephalon, MESH: Transcription Factors, Biological Evolution, MESH: Genes, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, MESH: Auditory Pathways, Brainstem, Hair cell, Sensory Receptor Cells, Neurogenesis, Nerve Tissue Proteins, MESH: Biological Evolution, Biology, Auditory cortex, hair cell, 03 medical and health sciences, Hair Cells, Auditory, evolution, medicine, Auditory system, Animals, Humans, Transcription factor, gene regulatory networks, Cochlea, MESH: Humans, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neurogenesis, Rhombencephalon, 030104 developmental biology, Gene Ontology, Genes, MESH: Ion Channels, Neuroscience, 030217 neurology & neurosurgery, Function (biology), Transcription Factors
Abstract

International audience; The genetic approach, based on the study of inherited forms of deafness, has proven to be particularly effective for deciphering the molecular mechanisms underlying the development of the peripheral auditory system, the cochlea and its afferent auditory neurons, and how this system extracts the physical parameters of sound. Although this genetic dissection has provided little information about the central auditory system, scattered data suggest that some genes may have a critical role in both the peripheral and central auditory systems. Here, we review the genes controlling the development and function of the peripheral and central auditory systems, focusing on those with demonstrated intrinsic roles in both systems and highlighting the current underappreciation of these genes. Their encoded products are diverse, from transcription factors to ion channels, as are their roles in the central auditory system, mostly evaluated in brainstem nuclei. We examine the on-togenetic and evolutionary mechanisms that may underlie their expression at different sites.

Published
2019
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3. Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, form a ternary complex and interact with membrane phospholipids

Author

Sylviane Hoos, Jean-Pierre Hardelin, Christine Petit, Vincent Michel, Patrick England, Anne Houdusse, Amel Bahloul, Sylvie Nouaille, Génétique et Physiologie de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique des Macromolécules et de leurs Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Institut Pasteur [Paris] (IP), Collège de France (CdF (institution)), This work was supported by LHW-Stiftung, Fondation Orange, Conny Maeva Foundation, ANR-05-MRAR-015-01, Raymonde and Guy Strittmatter Foundation (under the aegis of Fondation de France), FAUN Stiftung (Suchert Foundation). Funding to pay the Open Access Charge was provided by Unite de Genetique et Physiologie de l'Audition, Institut Pasteur, France., The authors thank Muriel Delepierre for NMR spectra, Raphaël Etournay and Alexandre Chenal for their advice in the preparation of LUV, Beatrice Amigues for myosin VIIa tail preparation, Bruno Baron for circular dichroism experiments, Jacqueline Levilliers for her help in the manuscript preparation and the staff of Dynamic Imaging platform of the Pasteur Institute., ANR-05-MRAR-0015,Usher type I,Physiopathologie du syndrome de Usher de type I : de la structure de la myosine VIIa et de l'harmonine à leur fonction dans les cellules ciliées auditives(2005), ENGLAND, Patrick, and Programme pluriannuel de recherche sur les maladies rares - Physiopathologie du syndrome de Usher de type I : de la structure de la myosine VIIa et de l'harmonine à leur fonction dans les cellules ciliées auditives - - Usher type I2005 - ANR-05-MRAR-0015 - MRAR - VALID

Subjects
Male, MESH: Cytoskeletal Proteins, [SDV]Life Sciences [q-bio], Cell Cycle Proteins, Plasma protein binding, MESH: Mice, Knockout, MESH: Cadherins, Mice, MESH: Protein Structure, Tertiary, Myosin, MESH: Hair Cells, Auditory, MESH: Animals, Ternary complex, Phospholipids, Genetics (clinical), Mice, Knockout, MESH: Protein Multimerization, Articles, General Medicine, Cadherins, [SDV] Life Sciences [q-bio], Biochemistry, Myosin VIIa, Female, Usher Syndromes, Protein Binding, Gene isoform, PDZ domain, MESH: Carrier Proteins, macromolecular substances, Myosins, Biology, Cell Line, MESH: Cell Cycle Proteins, Hair Cells, Auditory, otorhinolaryngologic diseases, Genetics, Molecular motor, Animals, Humans, MESH: Myosin VIIa, MESH: Protein Binding, MESH: Usher Syndromes, MESH: Mice, Molecular Biology, MESH: Phospholipids, MESH: Humans, Cadherin, MESH: Myosins, MESH: Male, Protein Structure, Tertiary, MESH: Cell Line, Cytoskeletal Proteins, Disease Models, Animal, Cytoplasm, Biophysics, sense organs, Protein Multimerization, MESH: Disease Models, Animal, Carrier Proteins, MESH: Female
Abstract

International audience; Cadherin-23 is a component of early transient lateral links of the auditory sensory cells' hair bundle, the mechanoreceptive structure to sound. This protein also makes up the upper part of the tip links that control gating of the mechanoelectrical transduction channels. We addressed the issue of the molecular complex that anchors these links to the hair bundle F-actin core. By using surface plasmon resonance assays, we show that the cytoplasmic regions of the two cadherin-23 isoforms that do or do not contain the exon68encoded peptide directly interact with harmonin, a submembrane PDZ (post-synaptic density, disc large, zonula occludens) domain-containing protein, with unusually high affinity. This interaction involves the harmonin Nter-PDZ1 supramodule, but not the C-terminal PDZ-binding motif of cadherin-23. We establish that cadherin-23 directly binds to the tail of myosin VIIa. Moreover, cadherin-23, harmonin and myosin VIIa can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links. We also show that the cadherin-23 cytoplasmic region, harmonin and myosin VIIa interact with phospholipids on synthetic liposomes. Harmonin and the cytoplasmic region of cadherin-23, both independently and as a binary complex, can bind specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2), which may account for the role of this phospholipid in the adaptation of mechanoelectrical transduction in the hair bundle. The distributions of cadherin-23, harmonin, myosin VIIa and PI(4,5)P 2 in the growing and mature auditory hair bundles as well as the abnormal locations of harmonin and myosin VIIa in cadherin-23 null mutant mice strongly support the functional relevance of these interactions.

Published
2010
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4. Genetics of auditory mechano-electrical transduction

Author

Nicolas Michalski, Christine Petit, Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), The authors’ research is supported by grants from the European Research council (ERC-2011-AdG 294570 HAIRBUNDLE), the Agence nationale pour la recherche (EARMEC—ANR 11 BSV5 011 02), the LABEX LIFESENSES (reference ANR-10-LABX-65) supported by French state funds within the Investissementsd’Avenir programme under reference ANR-11-IDEX-0004-02, BNPParibas and LHW Stiftung, ANR-11-BSV5-0011,EARMEC,Propriétés mécaniques, actives et passives, de la touffe ciliaire des cellules mécano-sensorielles ciliées le long de l'axe tonotopique de la cochlée des mammifères.(2011), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), Collège de France - Chaire Génétique et physiologie cellulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), michalski, nicolas, BLANC - Propriétés mécaniques, actives et passives, de la touffe ciliaire des cellules mécano-sensorielles ciliées le long de l'axe tonotopique de la cochlée des mammifères. - - EARMEC2011 - ANR-11-BSV5-0011 - BLANC - VALID, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, and Assembling the puzzle of the operating auditory hair bundle - HAIRBUNDLE - - EC:FP7:ERC2012-12-01 - 2017-11-30 - 294570 - VALID

Subjects
Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clinical Biochemistry, MESH: Molecular Motor Proteins, Action Potentials, Mechanotransduction, Cellular, Membrane Potentials, 0302 clinical medicine, Hearing, MESH: Hair Cells, Auditory, MESH: Animals, Neurogenetics, MESH: Action Potentials, Genetics, 0303 health sciences, Molecular Motor Proteins, Hair bundle, Cochlea, Molecular network, medicine.anatomical_structure, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Hair cell, MESH: Membrane Proteins, MESH: Pressure, Transduction (physiology), Mechano-electrical transduction, Biology, 03 medical and health sciences, Physiology (medical), Hair Cells, Auditory, Pressure, medicine, otorhinolaryngologic diseases, Animals, Humans, MESH: Membrane Potentials, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH: Hearing, 030304 developmental biology, Invited Review, MESH: Humans, MESH: Mechanotransduction, Cellular, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Membrane Proteins, Human physiology, Mechano electrical transduction, sense organs, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; The hair bundles of cochlear hair cells play a central role in the auditory mechano-electrical transduction (MET) process. The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea. In contrast, human and mouse genetics have proven to be particularly powerful. The study of inherited forms of deafness led to the discovery of several essential proteins of the MET machinery, which are currently used as entry points to decipher the associated molecular networks. Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current. Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.

Published
2015
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5. Pattern formation in the lateral line of zebrafish

Author

Christine Thisse, Nicolas Gompel, Alain Ghysen, Bernard Thisse, Christine Dambly-Chaudière, Nicolas Cubedo, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurogénétique, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR122, Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire, and Université Louis Pasteur - Strasbourg I

Subjects
Flank, Embryology, Time Factors, MESH: Neurons, 0302 clinical medicine, Cell Movement, MESH: Gene Expression Regulation, Developmental, MESH: Hair Cells, Auditory, MESH: Animals, MESH: Dextrans, MESH: Fluorescein, Zebrafish, MESH: Cell Movement, [SDV.BDD]Life Sciences [q-bio]/Development Biology, In Situ Hybridization, Neurons, 0303 health sciences, Microscopy, Video, Gene Expression Regulation, Developmental, Dextrans, Anatomy, MESH: Fluorescent Dyes, medicine.anatomical_structure, embryonic structures, %22">Fish , Fluorescein, Hair cell, MESH: Cell Nucleus, animal structures, Ultraviolet Rays, Pattern formation, Mitosis, Cell lineage, Biology, 03 medical and health sciences, MESH: In Situ Hybridization, Hair Cells, Auditory, medicine, Animals, Primordium, Cell Lineage, MESH: Zebrafish, 030304 developmental biology, Fluorescent Dyes, Cell Nucleus, MESH: Time Factors, MESH: Cell Lineage, MESH: Mitosis, biology.organism_classification, MESH: Microscopy, Video, MESH: Ultraviolet Rays, Line (text file), 030217 neurology & neurosurgery, Developmental Biology
Abstract

The lateral line of fish and amphibians is a sensory system that comprises a number of individual sense organs, the neuromasts, arranged in a defined pattern on the surface of the body. A conspicuous part of the system is a line of organs that extends along each flank (and which gave the system its name). At the end of zebrafish embryogenesis, this line comprises 7-8 neuromasts regularly spaced between the ear and the tip of the tail. The neuromasts are deposited by a migrating primordium that originates from the otic region. Here, we follow the development of this pattern and show that heterogeneities within the migrating primordium prefigure neuromast formation.

Published
2001
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6. Neuronal differences prefigure somatotopy in the zebrafish lateral line

Author

Christine Dambly-Chaudière, Alain Ghysen, Nicolas Gompel, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurogénétique, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR122

Subjects
Central projection, Neurite, Lateral line, Growth Cones, MESH: Microscopy, Fluorescence, Sensory system, MESH: Brain, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Hair Cells, Auditory, Neural Pathways, Animals, MESH: Hair Cells, Auditory, Cell Lineage, MESH: Animals, Neurons, Afferent, MESH: Zebrafish, 10. No inequality, MESH: Cell Movement, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Molecular Biology, Zebrafish, Fluorescent Dyes, 030304 developmental biology, 0303 health sciences, biology, MESH: Neurons, Afferent, MESH: Neural Pathways, Brain, MESH: Immunohistochemistry, MESH: Growth Cones, Anatomy, MESH: Cell Lineage, MESH: Fluorescent Dyes, biology.organism_classification, Immunohistochemistry, Microscopy, Fluorescence, nervous system, Line (text file), 030217 neurology & neurosurgery, Developmental Biology
Abstract

The central projection of the fish lateral line displays somatotopic ordering. In order to know when and how this ordering is established, we have labelled single sensory neurones and followed the growth of their neurites. We show that the neuromast cells and the corresponding neurones are not related by a fixed lineage, and also that somatotopic differences between anterior and posterior line neurones, and among neurones of the posterior line,are present before innervation of the sense organs. We propose that the position of the central projection defines the peripheral position that the neurone will innervate.

Published
2001
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7. Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia

Author

Dominique Weil, Sébastien Chardenoux, Paul Avan, Vincent Michel, Nicolas Michalski, Olinda Alegria-Prévot, Marcio Do Cruzeiro, Isabelle Perfettini, Guy P. Richardson, Richard J. Goodyear, Isabelle Foucher, Elisa Caberlotto, Jean-Pierre Hardelin, Amel Bahloul, Christine Petit, Elise Pepermans, Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Université Pierre et Marie Curie - Paris 6 (UPMC), Génétique des Déficits Sensoriels, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Life Sciences, University of Sussex, Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] (PRHTEC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe Biophysique Neurosensorielle [Neuro-Dol], Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), This work was supported by FAUN Stiftung (Suchert Foundation), Fondation Raymonde and Guy Strittmatter,LHW-Stiftung, the Conny Maeva Charitable Foundation, Fondation Orange, and the Louis-Jeantet Foundation. R.J.G. and G.P.R. are supported by The Wellcome Trust, Chaire Génétique et physiologie cellulaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), michalski, nicolas, Génétique et Physiologie de l'Audition, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Collège de France ( CdF ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] ( PRHTEC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Neuro-Dol ( Neuro-Dol ), Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Neuro-Dol - Clermont Auvergne ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Université Clermont Auvergne ( UCA ), and Collège de France ( CdF )

Subjects
Scaffold protein, MESH: Signal Transduction, MESH: Protein Precursors, MESH : Immunohistochemistry, [SDV]Life Sciences [q-bio], MESH : Actins, Fluorescent Antibody Technique, MESH : Analysis of Variance, MESH: Mice, Knockout, MESH: Cadherins, Polymerization, Mice, 0302 clinical medicine, MESH: Genetic Vectors, MESH: Hair Cells, Auditory, MESH : Polymerization, MESH: Animals, MESH: Nerve Tissue Proteins, Mechanotransduction, MESH : Protein Precursors, MESH : Nerve Tissue Proteins, MESH: Fluorescent Antibody Technique, Mice, Knockout, 0303 health sciences, Multidisciplinary, MESH: Electrophysiology, Cilium, Biological Sciences, Cadherins, Immunohistochemistry, MESH : Genetic Vectors, Cell biology, [SDV] Life Sciences [q-bio], Electrophysiology, medicine.anatomical_structure, MESH: Polymerization, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Cadherins, Transduction (physiology), Engineering sciences. Technology, Signal Transduction, MESH : Microscopy, Electron, Scanning, MESH: Microscopy, Electron, Scanning, Genetic Vectors, Cadherin Related Proteins, Nerve Tissue Proteins, Biology, MESH: Actins, MESH : Cilia, 03 medical and health sciences, MESH : Electrophysiology, MESH: Cilia, MESH: Analysis of Variance, MESH : Mice, Hair Cells, Auditory, medicine, otorhinolaryngologic diseases, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cilia, Protein Precursors, MESH : Hair Cells, Auditory, MESH: Mice, Actin, 030304 developmental biology, MESH : Signal Transduction, Analysis of Variance, [ SDV ] Life Sciences [q-bio], Stereocilia, MESH: Immunohistochemistry, Actins, MESH : Fluorescent Antibody Technique, Cytoplasm, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Microscopy, Electron, Scanning, MESH : Mice, Knockout, MESH : Animals, sense organs, Tip link, 030217 neurology & neurosurgery
Abstract

The mechanotransducer channels of auditory hair cells are gated by tip-links, oblique filaments that interconnect the stereocilia of the hair bundle. Tip-links stretch from the tips of stereocilia in the short and middle rows to the sides of neighboring, taller stereocilia. They are made of cadherin-23 and protocadherin-15, products of the Usher syndrome type 1 genes USH1D and USH1F, respectively. In this study we address the role of sans, a putative scaffold protein and product of the USH1G gene. In Ush1g −/− mice, the cohesion of stereocilia is disrupted, and both the amplitude and the sensitivity of the transduction currents are reduced. In Ush1g fl/fl Myo15-cre +/− mice, the loss of sans occurs postnatally and the stereocilia remain cohesive. In these mice, there is a decrease in the amplitude of the total transducer current with no loss in sensitivity, and the tips of the stereocilia in the short and middle rows lose their prolate shape, features that can be attributed to the loss of tip-links. Furthermore, stereocilia from these rows undergo a dramatic reduction in length, suggesting that the mechanotransduction machinery has a positive effect on F-actin polymerization. Sans interacts with the cytoplasmic domains of cadherin-23 and protocadherin-15 in vitro and is absent from the hair bundle in mice defective for either of the two cadherins. Because sans localizes mainly to the tips of short- and middle-row stereocilia in vivo, we conclude that it belongs to a molecular complex at the lower end of the tip-link and plays a critical role in the maintenance of this link.

Published
2011
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8. Stereocilin connects outer-hair-cell stereocilia to one another and to the tectorial membrane

Author

Nicolas Michalski, Dominique Weil, Richard J. Goodyear, Elisabeth Verpy, Carine Houdon, Christine Petit, Guy P. Richardson, Michel Leibovici, Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), School of Life Sciences, University of Sussex, Grant sponsor: European Commission FP6 Integrated Project EuroHear, Grant number: LSHG-CT-2004-512063, Grant sponsor: Fondation Raymonde & Guy Strittmatter – Fondation de France, Grant sponsor: Société Réunica-Prévoyance, Grant sponsor: The Wellcome Trust, Grant number: 071394/Z/03/Z., European Project, and Chaire Génétique et physiologie cellulaire

Subjects
Stereocilia (inner ear), cochlea, MESH: Mice, Knockout, Mechanotransduction, Cellular, hair-bundle cohesiveness, Mice, 0302 clinical medicine, horizontal top connectors, MESH: Hair Cells, Auditory, MESH: Animals, MESH: Proteins, Mice, Knockout, 0303 health sciences, MESH: Electrophysiology, General Neuroscience, MESH: Tectorial Membrane, Anatomy, Kinocilium, Immunohistochemistry, Cell biology, Electrophysiology, medicine.anatomical_structure, Intercellular Signaling Peptides and Proteins, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Hair cell, organ of Corti, STRC, Tectorial Membrane, Tectorial membrane, Guinea Pigs, Biology, INDEXING TERMS: inner ear, Article, MESH: Guinea Pigs, 03 medical and health sciences, MESH: Cilia, Hair Cells, Auditory, medicine, otorhinolaryngologic diseases, Animals, attachment links, Cilia, MESH: Mice, Vestibular Hair Cell, Cochlea, 030304 developmental biology, MESH: Mechanotransduction, Cellular, Proteins, MESH: Immunohistochemistry, Grant sponsor: Fondation Raymonde & Guy Strittmatter – Fondation de France, Organ of Corti, sense organs, 030217 neurology & neurosurgery
Abstract

International audience; Stereocilin is defective in a recessive form of deafness, DFNB16. We studied the distribution of stereocilin in the developing and mature mouse inner ear and analyzed the consequences of its absence in stereocilin-null (Strc(-/-)) mice that suffer hearing loss starting at postnatal day 15 (P15) and progressing until P60. Using immunofluorescence and immunogold electron microscopy, stereocilin was detected in association with two cell surface specializations specific to outer hair cells (OHCs) in the mature cochlea: the horizontal top connectors that join the apical regions of adjacent stereocilia within the hair bundle, and the attachment links that attach the tallest stereocilia to the overlying tectorial membrane. Stereocilin was also detected around the kinocilium of vestibular hair cells and immature OHCs. In Strc(-/-) mice the OHC hair bundle was structurally and functionally normal until P9. Top connectors, however, did not form and the cohesiveness of the OHC hair bundle progressively deteriorated from P10. The stereocilia were still interconnected by tip links at P14, but these progressively disappeared from P15. By P60 the stereocilia, still arranged in a V-shaped bundle, were fully disconnected from each other. Stereocilia imprints on the lower surface of the tectorial membrane were also not observed in Strc(-/-) mice, thus indicating that the tips of the tallest stereocilia failed to be embedded in this gel. We conclude that stereocilin is essential to the formation of horizontal top connectors. We propose that these links, which maintain the cohesiveness of the mature OHC hair bundle, are required for tip-link turnover.

Published
2011
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9. Primary epithelioid sarcoma of bone: report of a unique case, with immunohistochemical and fluorescent in situ hybridization confirmation of INI1 deletion

Author

Brigitte Vaunois, Andrew L. Folpe, Anne Valérie Decouvelaere, Florence Pedeutour, Delphine Raoux, Michel Peoc'h, Département de pathologie, CHU Saint Etienne, CHU Saint-Etienne-Hôpital Bellevue, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Université de Lyon

Subjects
Pathology, Chromosomal Proteins, Non-Histone, CD34, MESH: Plant Roots, Chondroblastoma, 0302 clinical medicine, Primary Epithelioid Sarcoma, MESH: Hair Cells, Auditory, MESH: Animals, MESH: In Situ Hybridization, Fluorescence, [SDV.BDD]Life Sciences [q-bio]/Development Biology, In Situ Hybridization, Fluorescence, 0303 health sciences, medicine.diagnostic_test, MESH: Drugs, Chinese Herbal, Soft tissue sarcoma, Sarcoma, MESH: Transcription Factors, SMARCB1 Protein, MESH: Bone Neoplasms, Immunohistochemistry, MESH: Keratinocytes, 3. Good health, DNA-Binding Proteins, 030220 oncology & carcinogenesis, MESH: Cell Division, Osteosarcoma, Female, Anatomy, MESH: Tomography, X-Ray Computed, Epithelioid cell, MESH: Cells, Cultured, Adult, medicine.medical_specialty, Epithelioid sarcoma, MESH: Molecular Structure, Bone Neoplasms, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, MESH: Skin, MESH: Alkaloids, MESH: Chromosomal Proteins, Non-Histone, MESH: Isoquinolines, medicine, Biomarkers, Tumor, Humans, MESH: Mice, Inbred C3H, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Adult, MESH: Immunohistochemistry, medicine.disease, MESH: Gene Deletion, MESH: Fibroblasts, MESH: Sarcoma, MESH: Tumor Markers, Biological, Surgery, Tomography, X-Ray Computed, MESH: Female, MESH: DNA-Binding Proteins, Gene Deletion, Fluorescence in situ hybridization, Transcription Factors
Abstract

International audience; We report the clinical and pathologic features of, what is to the best of our knowledge, the first case of epithelioid sarcoma of bone. A 31-year-old woman with an unremarkable past medical history presented with pelvic pain and was found by computed tomography scan to have a destructive 5 cm, partially calcified intraosseous lesion of the iliac bone. Histologically, the tumor consisted of relatively uniform but clearly malignant-appearing epithelioid cells, with scattered rhabdoid-appearing cells. A hyalinized to partially calcified matrix was present between the tumor cells, with a "chickenwire" pattern of calcification. By immunohistochemistry, the neoplastic cells expressed cytokeratins, vimentin, epithelial membrane antigen and CD34, and showed complete loss of INI1 protein expression. Fluorescence in situ hybridization showed homozygous deletion of the INI1 gene. An extensive clinical and radiographic workup did not show evidence of a soft tissue tumor, and the diagnosis of a primary epithelioid sarcoma of bone was made. After this, the patient underwent a complete resection of her tumor, and is currently disease free, 6 months after surgery. These extremely rare tumors must be rigorously distinguished from other more common tumors of bone, in particular, chondroblastoma and osteosarcoma. Awareness that epithelioid sarcoma may occur in bone, careful histologic evaluation and ancillary immunohistochemistry for epithelial markers, CD34 and INI1 protein should allow for recognition of such tumors. Study of additional cases of primary epithelioid sarcoma of bone will be necessary to better understand its clinical behavior.

Published
2009
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10. Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice

Author

Michel Eybalin, Richard J.H. Smith, Theru A. Sivakumaran, Tobias Moser, Marci M. Lesperance, Régis Nouvian, Salah El Mestikawy, Tiphaine Bersot, Jean-Luc Puel, Marc Lenoir, Benjamin Delprat, Jana M. Van Rybroek, Guy Rebillard, S. Emery, Bénédicte Amilhon, Bruno Giros, Jérôme Ruel, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1), Division of Pediatric Otolaryngology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, InnerEarLab, Department of Otolaryngology and Center for Molecular Physiology of the Brain-Georg-August-University = Georg-August-Universität Göttingen, Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Otolaryngology and Head and Neck Surgery, University of Iowa [Iowa City], Bernstein Center for Computational Neuroscience, Georg-August-University = Georg-August-Universität Göttingen, Department of Otolaryngology and Center for Molecular Physiology of the Brain-University of Göttingen - Georg-August-Universität Göttingen, University of Göttingen - Georg-August-Universität Göttingen, and Hamel, Christian

Subjects
Deafness, Ribbon synapse, MESH: Mice, Knockout, MESH: Vesicular Glutamate Transport Proteins, Linkage Disequilibrium, Mice, 0302 clinical medicine, Vesicular Glutamate Transport Proteins, MESH: Hair Cells, Auditory, Genetics(clinical), MESH: Animals, Nonsyndromic deafness, MESH: Models, Genetic, 10. No inequality, Genetics (clinical), Mice, Knockout, Genetics, 0303 health sciences, Genome, MESH: Amino Acid Transport Systems, Acidic, MESH: Polymorphism, Single Nucleotide, Glutamate receptor, Chromosome Mapping, Cell biology, medicine.anatomical_structure, SLC17A8, MESH: Linkage Disequilibrium, Sensorineural hearing loss, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Hair cell, MESH: Mutation, Amino Acid Transport Systems, Acidic, MESH: Deafness, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Hair Cells, Auditory, otorhinolaryngologic diseases, medicine, Animals, Humans, MESH: Genome, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Mice, Cochlea, Spiral ganglion, 030304 developmental biology, MESH: Humans, Models, Genetic, medicine.disease, Disease Models, Animal, Mutation, MESH: Disease Models, Animal, MESH: Chromosome Mapping, 030217 neurology & neurosurgery
Abstract

International audience; Autosomal-dominant sensorineural hearing loss is genetically heterogeneous, with a phenotype closely resembling presbycusis, the most common sensory defect associated with aging in humans. We have identified SLC17A8, which encodes the vesicular glutamate transporter-3 (VGLUT3), as the gene responsible for DFNA25, an autosomal-dominant form of progressive, high-frequency nonsyndromic deafness. In two unrelated families, a heterozygous missense mutation, c.632C-->T (p.A211V), was found to segregate with DFNA25 deafness and was not present in 267 controls. Linkage-disequilibrium analysis suggested that the families have a distant common ancestor. The A211 residue is conserved in VGLUT3 across species and in all human VGLUT subtypes (VGLUT1-3), suggesting an important functional role. In the cochlea, VGLUT3 accumulates glutamate in the synaptic vesicles of the sensory inner hair cells (IHCs) before releasing it onto receptors of auditory-nerve terminals. Null mice with a targeted deletion of Slc17a8 exon 2 lacked auditory-nerve responses to acoustic stimuli, although auditory brainstem responses could be elicited by electrical stimuli, and robust otoacoustic emissions were recorded. Ca(2+)-triggered synaptic-vesicle turnover was normal in IHCs of Slc17a8 null mice when probed by membrane capacitance measurements at 2 weeks of age. Later, the number of afferent synapses, spiral ganglion neurons, and lateral efferent endings below sensory IHCs declined. Ribbon synapses remaining by 3 months of age had a normal ultrastructural appearance. We conclude that deafness in Slc17a8-deficient mice is due to a specific defect of vesicular glutamate uptake and release and that VGLUT3 is essential for auditory coding at the IHC synapse.

Published
2008
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11. The lateral line microcosmos

Author

Alain Ghysen, Christine Dambly-Chaudière, Laboratoire de neurogénétique, and Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Lateral line, Embryonic Development, Models, Biological, Amphibians, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Planar cell polarity, Hair Cells, Auditory, MESH: Gene Expression Regulation, Developmental, Genetics, Animals, MESH: Embryonic Development, MESH: Hair Cells, Auditory, MESH: Animals, MESH: Lateral Line System, MESH: Zebrafish, Zebrafish, MESH: Cell Movement, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Body Patterning, 0303 health sciences, biology, MESH: Amphibia, Regeneration (biology), Fishes, MESH: Models, Biological, Cell Polarity, Gene Expression Regulation, Developmental, Anatomy, biology.organism_classification, Lateral Line System, MESH: Fishes, %22">Fish , MESH: Neuroglia, MESH: Cell Polarity, Neuroscience, Neuroglia, 030217 neurology & neurosurgery, Developmental Biology, MESH: Body Patterning
Abstract

The lateral-line system is a simple sensory system comprising a number of discrete sense organs, the neuromasts, distributed over the body of fish and amphibians in species-specific patterns. Its development involves fundamental biological processes such as long-range cell migration, planar cell polarity, regeneration, and post-embryonic remodeling. These aspects have been extensively studied in amphibians by experimental embryologists, but it is only recently that the genetic bases of this development have been explored in zebrafish. This review discusses progress made over the past few years in this field.

Published
2007
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12. A procedure to label inner ear afferent nerve endings for calcium imaging

Author

Samuel Boyer, Jean-Luc Puel, Jérôme Ruel, Christian Chabbert, Ruel, Jérôme, Physiopathologie et thérapie des déficits sensoriels et moteurs, and Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Stereocilia (inner ear), Action Potentials, Vestibular Nerve, Synaptic Transmission, MESH: Animals, Newborn, 0302 clinical medicine, Postsynaptic potential, MESH: Cochlea, MESH: Hair Cells, Auditory, MESH: Presynaptic Terminals, MESH: Animals, Organic Chemicals, Coloring Agents, MESH: Action Potentials, MESH: Spiral Ganglion, 0303 health sciences, MESH: Electrophysiology, General Neuroscience, MESH: Glutamic Acid, Anatomy, Vestibulocochlear Nerve, MESH: Fluorescent Dyes, Cochlea, Turtles, Electrophysiology, MESH: Staining and Labeling, medicine.anatomical_structure, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH: Calcium, MESH: Vestibular Nerve, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Vestibule, Labyrinth, Spiral Ganglion, MESH: Coloring Agents, MESH: Rats, Sensory Receptor Cells, Presynaptic Terminals, Glutamic Acid, MESH: Receptors, Sensory, Neurotransmission, Biology, MESH: Calcium Signaling, Vestibulocochlear nerve, MESH: Vestibulocochlear Nerve, 03 medical and health sciences, Calcium imaging, Hair Cells, Auditory, MESH: Synaptic Transmission, MESH: Turtles, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Calcium Signaling, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Rats, Wistar, Spiral ganglion, 030304 developmental biology, Fluorescent Dyes, Staining and Labeling, MESH: Organic Chemicals, MESH: Rats, Wistar, Rats, Animals, Newborn, MESH: Potassium, Potassium, Calcium, sense organs, MESH: Vestibule, Labyrinth, Neuroscience, Free nerve ending, 030217 neurology & neurosurgery
Abstract

International audience; Characterization of synaptic transmission between the inner ear sensory cells and primary neuron dendrites has been hampered by the limited access to the postsynaptic terminals. Because direct physiological recording of postsynaptic currents are difficult to achieve, no information regarding the synaptic and dendritic events are available. This is due to the small size of the postsynaptic afferent nerve endings that do not allow a clear identification, and thus compromise direct electrophysiological recordings of the buttons. To study the physiology of afferent nerve endings, we have developed a two-photon imaging technique in cochlear and vestibular slice preparations from neonatal rats and turtles. This technique is based on a retrograde labeling of afferent nerve endings with high-affinity calcium-sensitive dyes. Dye filling was achieved by 6 h application of the dextran-amine conjugate of calcium green-1. Calcium changes were measured in afferent nerve endings in line scan and time lap mode. To address recording in a near-physiological situation, iontophoretic application of K+ was performed in the area of the stereocilia whereas glutamate was applied at the basal pole of sensory hair cells. Both types of application cause a reversible and sustained increase of Ca2+ in the button of afferent nerve fibers. Typical recordings are presented and potential interests for pharmacological studies of inner ear sensory cell synapses are discussed.

Published
2004
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13. Microtubule-associated protein 2 (MAP2) expression during synaptic plasticity in the guinea pig cochlea

Author

Jean-Luc Puel, Sabine Ladrech, Jérôme Ruel, Marc Lenoir, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ruel, Jérôme

Subjects
Neurite, Guinea Pigs, Excitotoxicity, MESH: Neurons, Action Potentials, AMPA receptor, Neurotransmission, Biology, medicine.disease_cause, MESH: Synapses, MESH: Guinea Pigs, MESH: Vestibulocochlear Nerve, Microtubule-associated protein 2, Hair Cells, Auditory, MESH: Cochlea, Excitatory Amino Acid Agonists, medicine, Animals, MESH: Hair Cells, Auditory, Inner ear, MESH: Animals, MESH: Neuronal Plasticity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Cochlea, MESH: Action Potentials, Neurons, Neuronal Plasticity, MESH: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, MESH: Molecular Weight, Vestibulocochlear Nerve, Sensory Systems, Molecular Weight, MESH: Microtubule-Associated Proteins, medicine.anatomical_structure, nervous system, Synapses, Synaptic plasticity, Cochlear Microphonic Potentials, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Excitatory Amino Acid Agonists, Microtubule-Associated Proteins, Neuroscience, MESH: Female, MESH: Cochlear Microphonic Potentials
Abstract

International audience; The expression of different isoforms of microtubule-associated proteins 2 (MAP2), including the low molecular weight form MAP2c present mainly in developing neurons, was investigated in the primary auditory neurons after alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) perfusion in the guinea pig cochlea. MAP2 expression appeared to be tightly regulated in the repairing neurons. Neurite regrowth seems to involve the MAP2c isoform. In cochlear neurons, mechanisms involved in the period of development might be reactivated after excitotoxic injury in the mature cochlea.

Published
2003

14. Vezatin, a novel transmembrane protein, bridges myosin VIIA to the cadherin-catenins complex

Author

Uwe Wolfrum, Aziz El-Amraoui, Marc Lecuit, Christine Petit, Saaid Safieddine, Isabelle Perfettini, Polonca Küssel-Andermann, Pascale Cossart, Sylvie Nouaille, Génétique des Déficits sensoriels, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules, Institut Pasteur [Paris], Johannes Gutenberg - Universität Mainz (JGU), This work was supported by grants from the EC (QLG2-CT-1999-00988), Retina-France, A. & M. Suchert and Forschung contra Blindheit-Initiative Usher Syndrome, a C. & J.-P. Bernais donation, Deutsche Forschungsgemeinschaft (Wo 548/3-1/2 and Wo 548/4-1) (U.W.), FAUN-Stiftung, Nürnberg (U.W.) and the Pasteur Weizmann Joint Research Program (P.C.)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)

Subjects
MESH: Cytoskeletal Proteins, MESH: alpha Catenin, Stereocilia (inner ear), [SDV]Life Sciences [q-bio], MESH: Amino Acid Sequence, Deafness, MESH: Cadherins, Mice, MESH: Protein Structure, Tertiary, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Myosin, MESH: Hair Cells, Auditory, MESH: Animals, Cytoskeleton, 0303 health sciences, FERM domain, General Neuroscience, MESH: Alternative Splicing, Articles, Cadherins, Cell biology, medicine.anatomical_structure, Intercellular Junctions, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Myosin VIIa, Hair cell, MESH: Membrane Proteins, MESH: Dyneins, Protein Binding, MESH: Mutation, Macromolecular Substances, Molecular Sequence Data, MESH: Deafness, macromolecular substances, Biology, In Vitro Techniques, Myosins, General Biochemistry, Genetics and Molecular Biology, Cell Line, Adherens junction, 03 medical and health sciences, Hair Cells, Auditory, medicine, otorhinolaryngologic diseases, Animals, Humans, MESH: Myosin VIIa, MESH: Protein Binding, Amino Acid Sequence, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: In Vitro Techniques, MESH: Molecular Sequence Data, MESH: Humans, General Immunology and Microbiology, Cadherin, Dyneins, Membrane Proteins, MESH: Macromolecular Substances, MESH: Myosins, Actin cytoskeleton, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Protein Structure, Tertiary, MESH: Cell Line, Alternative Splicing, Cytoskeletal Proteins, Mutation, sense organs, 030217 neurology & neurosurgery, alpha Catenin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Intercellular Junctions
Abstract

International audience; Defects in myosin VIIA are responsible for deafness in the human and mouse. The role of this unconventional myosin in the sensory hair cells of the inner ear is not yet understood. Here we show that the C-terminal FERM domain of myosin VIIA binds to a novel transmembrane protein, vezatin, which we identi®ed by a yeast two-hybrid screen. Vezatin is a ubiquitous protein of adherens cell±cell junctions, where it interacts with both myosin VIIA and the cadherin±catenins complex. Its recruitment to adherens junctions implicates the C-terminal region of a-catenin. Taken together, these data suggest that myosin VIIA, anchored by vezatin to the cadherin±catenins complex, creates a tension force between adherens junctions and the actin cytoskeleton that is expected to strengthen cell±cell adhesion. In the inner ear sensory hair cells vezatin is, in addition, concentrated at another membrane±membrane interaction site, namely at the ®brillar links interconnecting the bases of adjacent stereocilia. In myosin VIIA-defective mutants, inactivity of the vezatin±myosin VIIA complex at both sites could account for splaying out of the hair cell stereocilia.

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