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

  • Defourny J
  • Poirrier A
  • Lallemend F
 et al. 
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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.

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Authors

  • Anne-Lise PoirrierCHU de Liege - Hopital du Sart Tilman

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  • Jean Defourny

  • Francois Lallemend

  • Susana Mateo Sánchez

  • Jakob Neef

  • Pierre Vanderhaeghen

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