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PMID: 11152640 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Development (Cambridge, England) ·Vol. 128 ·No. 3 ·2001-02-00 ·Pages 417-26

Kim WY, Fritzsch B, Serls A, Bakel LA, Huang EJ, Reichardt LF, Barth DS, Lee JE

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.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors Cell Death Cell Movement Cell Survival Cochlea/growth & development,innervation,pathology,ultrastructure Deafness/genetics,physiopathology Evoked Potentials, Auditory/genetics,physiology Gene Deletion Gene Expression Regulation, Developmental Genes, Reporter Hair Cells, Auditory, Inner/growth & development,metabolism,pathology,ultrastructure Helix-Loop-Helix Motifs Histocytochemistry In Situ Hybridization In Situ Nick-End Labeling Mice Mice, Knockout Microscopy, Electron Nerve Tissue Proteins/chemistry,genetics,physiology Neural Pathways/growth & development,pathology Receptor, trkB/genetics,metabolism Receptor, trkC/genetics,metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors Nerve Tissue Proteins Neurogenic differentiation factor 1 Receptor, trkB Receptor, trkC
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kim W Y
Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Fritzsch B
Serls A
Bakel L A
Huang E J
Reichardt L F
Barth D S
Lee J E
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
Published
2001-02-00
Pages
417-26
Language
English
Region
England
NLM ID
8701744
PMCID
PMC2710102
Subset
IM
Grants
NINDS NIH HHS · P01 NS016033 · United States
NINDS NIH HHS · P01 NS016033-17A10014 · United States
NIDCD NIH HHS · 2P01 DC00215 · United States
NINDS NIH HHS · R01NS35118 · United States
External Links
PubMed source PMC Full Text View journal details
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