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Disorganized Innervation and Neuronal Loss in the Inner Ear of Slitrk6-Deficient Mice
Journal article   Open access   Peer reviewed

Disorganized Innervation and Neuronal Loss in the Inner Ear of Slitrk6-Deficient Mice

Kei-ichi Katayama, Azel Zine, Maya Ota, Yoshifumi Matsumoto, Takashi Inoue, Bernd Fritzsch and Jun Aruga
PloS one, Vol.4(11), pp.A151-A162
11/11/2009
DOI: 10.1371/journal.pone.0007786
PMCID: PMC2777407
PMID: 19936227
url
https://doi.org/10.1371/journal.pone.0007786View
Published (Version of record) Open Access

Abstract

Slitrks are type I transmembrane proteins that share conserved leucine-rich repeat domains similar to those in the secreted axonal guidance molecule Slit. They also show similarities to Ntrk neurotrophin receptors in their carboxy-termini, sharing a conserved tyrosine residue. Among 6 Slitrk family genes in mammals, Slitrk6 has a unique expression pattern, with strong expression in the sensory epithelia of the inner ear. We generated Slitrk6 -knockout mice and investigated the development of their auditory and vestibular sensory organs. Slitrk6 -deficient mice showed pronounced reduction in the cochlear innervation. In the vestibule, the innervation to the posterior crista was often lost, reduced, or sometimes misguided. These defects were accompanied by the loss of neurons in the spiral and vestibular ganglia. Cochlear sensory epithelia from Slitrk6 -knockout mice have reduced ability in promoting neurite outgrowth of spiral ganglion neurons. Indeed the Slitrk6 -deficient inner ear showed a mild but significant decrease in the expression of Bdnf and Ntf3 , both of which are essential for the innervation and survival of sensory neurons. In addition, the expression of Ntrk receptors, including their phosphorylated forms was decreased in Slitrk6 -knockout cochlea. These results suggest that Slitrk6 promotes innervation and survival of inner ear sensory neurons by regulating the expression of trophic and/or tropic factors including neurotrophins from sensory epithelia.
Genetics and Genomics Developmental Biology Neuroscience

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