Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells
2013 (English)In: Nature Communications, ISSN 2041-1723, Vol. 4, 1438- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 4, 1438- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-199555DOI: 10.1038/ncomms2445ISI: 000316616400014OAI: oai:DiVA.org:uu-199555DiVA: diva2:620072