NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development

A key factor in the genetically programmed development of the nervous syste m is the death of massive numbers of neurons. Therefore, genetic mechanisms governing cell survival are of fundamental importance to developmental neu roscience. We report that inner ear sensory neurons are dependent on a basi c helix-loop-helix transcription factor called NeuroD for survival during d ifferentiation. Mice lacking NeuroD protein exhibit no auditory evoked pote ntials, reflecting a profound deafness. DiI fiber staining, immunostaining and cell death assays reveal that the deafness is due to the failure of inn er ear sensory neuron survival during development. The affected inner ear s ensory neurons fail to express neurotrophin receptors, TrkB and T-kC, sugge sting that the ability of NeuroD to support neuronal survival may be direct ly mediated through regulation of responsiveness to the neurotrophins.