NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea

Lino Tessarollo; Vincenzo Coppola; Bernd Fritzsch

doi:10.1523/JNEUROSCI.5514-03.2004

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NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea

Journal article

Open access

Peer reviewed

NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea

Lino Tessarollo, Vincenzo Coppola and Bernd Fritzsch

The Journal of neuroscience, Vol.24(10), pp.2575-2584

03/10/2004

DOI: 10.1523/JNEUROSCI.5514-03.2004

PMCID: PMC3901528

PMID: 15014133

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Abstract

Survival of inner ear sensory neurons depends on two neurotrophins, BDNF and NT-3, and their respective receptors, TrkB and TrkC. Because both receptors are present in the same neuron, it has been suggested that BDNF and NT-3 are functionally redundant in promoting neuronal survival. Knock-in of one ligand into the locus of the other one confirmed this hypothesis for the cochlea, leaving open the question of why two neurotrophins are required for proper innervation of the mammalian ear. Here, we show that the precise spatiotemporal pattern of expression of the two neurotrophins is essential for proper patterning of the inner ear innervation. Mice expressing BDNF under the control of the NT-3 promoter develop exuberant projections of vestibular sensory neurons to the basal turn of the cochlea. This projection can be enhanced by combining the transgene with a null mutation of BDNF. However, vestibular fibers rerouted into the cochlea do not reach hair cells and remain outside the organ of Corti, suggesting a chemotactic role for neurotrophins on these fibers. Our data provide genetic evidence that neurotrophins in the ear exert both survival and axon guidance roles.

Brain-Derived Neurotrophic Factor - genetics

Hair Cells, Auditory - cytology

Cochlea - embryology

Cell Survival - genetics

Neurotrophin 3 - genetics

Axons - physiology

Vestibule, Labyrinth - metabolism

Cochlea - innervation

Nerve Fibers - physiology

Hair Cells, Auditory - physiology

Cochlea - metabolism

Gene Expression Regulation, Developmental

Mice, Mutant Strains

Vestibule, Labyrinth - embryology

Brain-Derived Neurotrophic Factor - biosynthesis

Cell Survival - physiology

Nerve Fibers - metabolism

Promoter Regions, Genetic

Mice, Inbred C57BL

Mice, Transgenic

Gestational Age

Animals

Vestibule, Labyrinth - innervation

Mice

Fluorescent Dyes

Details

Title: Subtitle: NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea
Creators: Lino Tessarollo - Neural Development Group, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21701, USA
Vincenzo Coppola
Bernd Fritzsch
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.24(10), pp.2575-2584
DOI: 10.1523/JNEUROSCI.5514-03.2004
PMID: 15014133
PMCID: PMC3901528
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Publisher: United States
Grant note: R01 DC005590 / NIDCD NIH HHS R01 DC005590-03 / NIDCD NIH HHS
Language: English
Date published: 03/10/2004
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070159402771

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