Abstract
A key factor in the genetically programmed development of the nervous system is the death of massive numbers of neurons. Therefore, genetic mechanisms governing cell survival are of fundamental importance to developmental neuroscience. We report that inner ear sensory neurons are dependent on a basic helix-loop-helix transcription factor called NeuroD for survival during differentiation. Mice lacking NeuroD protein exhibit no auditory evoked potentials, reflecting a profound deafness. DiI fiber staining, immunostaining and cell death assays reveal that the deafness is due to the failure of inner ear sensory neuron survival during development. The affected inner ear sensory neurons fail to express neurotrophin receptors, TrkB and TrkC, suggesting that the ability of NeuroD to support neuronal survival may be directly mediated through regulation of responsiveness to the neurotrophins.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Cell Death
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Cell Movement
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Cell Survival
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Cochlea / growth & development*
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Cochlea / innervation
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Cochlea / pathology
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Cochlea / ultrastructure
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Deafness / genetics*
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Deafness / physiopathology
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Evoked Potentials, Auditory / genetics
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Evoked Potentials, Auditory / physiology
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Gene Deletion*
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Gene Expression Regulation, Developmental
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Genes, Reporter
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Hair Cells, Auditory, Inner / growth & development
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Hair Cells, Auditory, Inner / metabolism
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Hair Cells, Auditory, Inner / pathology*
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Hair Cells, Auditory, Inner / ultrastructure
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Helix-Loop-Helix Motifs
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Histocytochemistry
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In Situ Hybridization
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In Situ Nick-End Labeling
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Mice
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Mice, Knockout
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Microscopy, Electron
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / physiology
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Neural Pathways / growth & development
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Neural Pathways / pathology
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Receptor, trkB / genetics
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Receptor, trkB / metabolism
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Receptor, trkC / genetics
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Receptor, trkC / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Nerve Tissue Proteins
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Neurogenic differentiation factor 1
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Receptor, trkB
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Receptor, trkC