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First published online August 18, 2003
doi: 10.1242/10.1242/dev.00676
RESEARCH ARTICLES: DEVELOPMENT AND DISEASE |
1 Tübingen Hearing Research Center (THRC), University of Tübingen,
Department of Otolaryngology, Molecular Neurobiology, Elfriede-Aulhorn-Strasse
5, D-72076 Tübingen
2 Center for Molecular Neurobiology Hamburg, University of Hamburg, Falkenried
94, D-20251 Hamburg, Germany
3 European Molecular Biology Laboratory, via Ramarini 32, 00016 Monterotondo,
Italy
* Author for correspondence (e-mail: marlies.knipper{at}uni-tuebingen.de)
Accepted 18 June 2003
Members of the neurotrophin gene family and their high-affinity Trk receptors control innervation of the cochlea during embryonic development. Lack of neurotrophin signalling in the cochlea has been well documented for early postnatal animals, resulting in a loss of cochlear sensory neurones and a region-specific reduction of target innervation along the tonotopic axis. However, how reduced neurotrophin signalling affects the innervation of the mature cochlea is currently unknown. Here, we have analysed the consequences of a lack of the TrkB receptor and its ligand, the neurotrophin brain-derived neurotrophic factor (Bdnf), in the late postnatal or adult cochlea using mouse mutants. During early postnatal development, mutant animals show a lack of afferent innervation of outer hair cells in the apical part of the cochlea, whereas nerve fibres in the basal part are maintained. Strikingly, this phenotype is reversed during subsequent maturation of the cochlea, which results in a normal pattern of outer hair cell innervation in the apex and loss of nerve fibres at the base in adult mutants. Measurements of auditory brain stem responses of these mice revealed a significant hearing loss. The observed innervation patterns correlate with opposing gradients of Bdnf and Nt3 expression in cochlear neurones along the tonotopic axis. Thus, the reshaping of innervation may be controlled by autocrine signalling between neurotrophins and their receptors in cochlear neurones. Our results indicate a substantial potential for re-innervation processes in the mature cochlea, which may also be of relevance for treatment of hearing loss in humans.
Key words: Bdnf, TrkB, Cochlea, Hearing loss, Mice
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