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Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

Author

Listed:
  • Jean Defourny

    (GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36)

  • Anne-Lise Poirrier

    (GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36
    CHU de Liège
    Present address: Royal National Throat Nose Ear Hospital, University College London, London, WC1X8DA, UK)

  • François Lallemend

    (Unit of Molecular Neurobiology, Karolinska Institute)

  • Susana Mateo Sánchez

    (GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36)

  • Jakob Neef

    (InnerEarLab, University of Göttingen Medical Center)

  • Pierre Vanderhaeghen

    (Institute of Interdisciplinary Research on Human and Molecular Biology (IRIBHM), Université Libre de Bruxelles (ULB))

  • Eduardo Soriano

    (Developmental Neurobiology and Regeneration Unit, Institut de Recerca Biomèdica (IRB) and University of Barcelona, Parc Científic de Barcelona)

  • Christiane Peuckert

    (Uppsala University, Box 593)

  • Klas Kullander

    (Uppsala University, Box 593)

  • Bernd Fritzsch

    (College of Liberal Arts and Sciences, University of Iowa)

  • Laurent Nguyen

    (GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36)

  • Gustave Moonen

    (GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36
    C.H.U. Sart Tilman, B35)

  • Tobias Moser

    (InnerEarLab, University of Göttingen Medical Center)

  • Brigitte Malgrange

    (GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36)

Abstract

Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

Suggested Citation

  • Jean Defourny & Anne-Lise Poirrier & François Lallemend & Susana Mateo Sánchez & Jakob Neef & Pierre Vanderhaeghen & Eduardo Soriano & Christiane Peuckert & Klas Kullander & Bernd Fritzsch & Laurent N, 2013. "Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2445
    DOI: 10.1038/ncomms2445
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    Cited by:

    1. Charles Petitpré & Louis Faure & Phoebe Uhl & Paula Fontanet & Iva Filova & Gabriela Pavlinkova & Igor Adameyko & Saida Hadjab & Francois Lallemend, 2022. "Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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