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 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.
Kim
W Y
WY
Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Fritzsch
B
B
Serls
A
A
Bakel
L A
LA
Huang
E J
EJ
Reichardt
L F
LF
Barth
D S
DS
Lee
J E
JE
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D016923:Cell Death; D002465:Cell Movement; D002470:Cell Survival; D003051:Cochlea / Q000254:growth & development* / Q000294:innervation / Q000473:pathology / Q000648:ultrastructure; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology; D005072:Evoked Potentials, Auditory / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006199:Hair Cells, Auditory, Inner / Q000254:growth & development / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018257:Helix-Loop-Helix Motifs; D006651:Histocytochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009434:Neural Pathways / Q000254:growth & development / Q000473:pathology; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D020813:Receptor, trkB; D020812:Receptor, trkC; C093564:Neurogenic differentiation factor 1