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

Afferent Pathways/metabolism; Animals; Auditory Threshold; Ephrin-A5/deficiency/genetics/metabolism; Gene Expression Regulation; Growth Cones/metabolism; Hair Cells, Auditory, Inner/metabolism; Immunohistochemistry; Mice; Microscopy, Confocal; Models, Biological; Receptor, EphA4/genetics/metabolism; Signal Transduction; Spiral Ganglion/cytology/innervation/metabolism; Synaptic Transmission

Abstract :

[en] 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.

Research Center/Unit :

Giga-Neurosciences - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology
Otolaryngology

Author, co-author :

Defourny, Jean

Poirrier, Anne-Lise

Lallemend, Francois

Mateo Sanchez, Susana ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie

Neef, Jakob

Vanderhaeghen, Pierre

Soriano, Eduardo

Peuckert, Christiane

Kullander, Klas

Fritzsch, Bernd

More authors (4 more)

Language :

English

Title :

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

Publication date :

2013

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Pages :

1438

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture
Fonds Léon Fredericq

Available on ORBi :

since 03 July 2013

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