Journal article
Spatial Shaping of Cochlear Innervation by Temporally Regulated Neurotrophin Expression
The Journal of neuroscience, Vol.21(16), pp.6170-6180
08/15/2001
DOI: 10.1523/JNEUROSCI.21-16-06170.2001
PMCID: PMC2710117
PMID: 11487640
Abstract
Previous work suggested qualitatively different effects of neurotrophin 3 (
NT-3
) in cochlear innervation patterning in different null mutants. We now show that all
NT-3
null mutants have a similar phenotype and lose all neurons in the basal turn of the cochlea. To understand these longitudinal deficits in neurotrophin mutants, we have compared the development of the deficit in the
NT-3
mutant to the spatial–temporal expression patterns of brain-derived neurotrophic factor (
BDNF
) and
NT-3,
using
lacZ
reporters in each gene and with expression of the specific neurotrophin receptors, trkB and trkC. In the
NT-3
mutant, almost normal numbers of spiral ganglion neurons form, but fiber outgrowth to the basal turn is eliminated by embryonic day (E) 13.5. Most neurons are lost between E13.5 and E15.5. During the period preceding apoptosis,
NT-3
is expressed in supporting cells, whereas
BDNF
is expressed mainly in hair cells, which become postmitotic in an apical to basal temporal gradient. During the period of neuronal loss, BDNF is absent from the basal cochlea, accounting for the complete loss of basal turn neurons in the
NT-3
mutant. The spatial gradients of neuronal loss in these two mutants appear attributable to spatial– temporal gradients of neurotrophin expression. Our immunocytochemical data show equal expression of their receptors,
Trk
B and
Trk
C, in spiral sensory neurons and thus do not relate to the basal turn loss. Mice in which
NT-3
was replaced by
BDNF
show a qualitative normal pattern of innervation at E13.5. This suggests that the pattern of expression of neurotrophins rather than their receptors is essential for the spatial loss of spiral sensory neurons in
NT-3
null mutants.
Details
- Title: Subtitle
- Spatial Shaping of Cochlear Innervation by Temporally Regulated Neurotrophin Expression
- Creators
- Isabel Fariñas - Program in Neuroscience, Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724Kevin R Jones - Department of Biology, University of Colorado, Boulder, Colorado 80309Lino Tessarollo - Neural Development Group, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21701Allison J Vigers - Department of Biology, University of Colorado, Boulder, Colorado 80309Eric Huang - Program in Neuroscience, Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724Martina Kirstein - Departamento de Biología Celular, Universidad de Valencia, 46100 Burjassot, SpainDominique C de Caprona - Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178Vincenzo Coppola - Neural Development Group, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21701Carey Backus - Program in Neuroscience, Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724Louis F Reichardt - Program in Neuroscience, Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724Bernd Fritzsch - Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.21(16), pp.6170-6180
- DOI
- 10.1523/JNEUROSCI.21-16-06170.2001
- PMID
- 11487640
- PMCID
- PMC2710117
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 08/15/2001
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070438402771
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