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

• Published in: Nature communications 2013, Vol.4 (1), p.1438-1438, Article 1438
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 631/378/2571; 631/378/2619/1533; 631/80/86; Afferent Pathways - metabolism; Animals; Auditory Threshold; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Ephrin-A5 - deficiency; Ephrin-A5 - genetics; Ephrin-A5 - metabolism; Ephrin-A5/deficiency/genetics/metabolism; Gene Expression Regulation; Growth Cones - metabolism; Hair Cells, Auditory, Inner - metabolism; Human health sciences; Humanities and Social Sciences; Immunohistochemistry; Klinisk medicin; Life sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Microscopy, Confocal; Models, Biological; multidisciplinary; Neurovetenskaper; Oto-rhino-laryngologie; Oto-rino-laryngologi; Otolaryngology; Receptor, EphA4 - genetics; Receptor, EphA4 - metabolism; Receptor, EphA4/genetics/metabolism; Science; Science (multidisciplinary); Sciences de la santé humaine; Sciences du vivant; Signal Transduction; Spiral Ganglion - cytology; Spiral Ganglion - innervation; Spiral Ganglion - metabolism; Spiral Ganglion/cytology/innervation/metabolism; Synaptic Transmission
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms2445

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. Cochlear inner and outer hair cells receive afferent innervation from type I and type II spiral ganglion neurons, respectively. Defourny et al . find that, in the absence of ephrin-A5 and its receptor EphA4, a subset of type I spiral ganglion neuron projections invade the outer hair cell area.