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

par Defourny, Jean;Poirrier, Anne-Lise;Lallemend, François;Mateo Sánchez, Susana;Neef, Jakob;Vanderhaeghen, Pierre ;Soriano, Eduardo;Peuckert, Christiane;Kullander, Klas;Fritzsch, Bernd;Nguyen, Laurent;Moonen, Gustave;Moser, Tobias;Malgrange, Brigitte
Référence Nature communications, 4, page (1438)
Publication Publié, 2013-02

Article révisé par les pairs

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Résumé :

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.