Journal article
Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers
Molecular neurobiology, Vol.57(12), pp.5307-5323
09/03/2020
DOI: 10.1007/s12035-020-02092-0
PMCID: PMC7547283
PMID: 32880858
Abstract
Ear development requires the transcription factors ATOH1 for hair cell differentiation and NEUROD1 for sensory neuron development. In addition, NEUROD1 negatively regulates Atoh1 gene expression. As we previously showed that deletion of the Neurod1 gene in the cochlea results in axon guidance defects and excessive peripheral innervation of the sensory epithelium, we hypothesized that some of the innervation defects may be a result of abnormalities in NEUROD1 and ATOH1 interactions. To characterize the interdependency of ATOH1 and NEUROD1 in inner ear development, we generated a new Atoh1/Neurod1 double null conditional deletion mutant. Through careful comparison of the effects of single Atoh1 or Neurod1 gene deletion with combined double Atoh1 and Neurod1 deletion, we demonstrate that NEUROD1-ATOH1 interactions are not important for the Neurod1 null innervation phenotype. We report that neurons lacking Neurod1 can innervate the flat epithelium without any sensory hair cells or supporting cells left after Atoh1 deletion, indicating that neurons with Neurod1 deletion do not require the presence of hair cells for axon growth. Moreover, transcriptome analysis identified genes encoding axon guidance and neurite growth molecules that are dysregulated in the Neurod1 deletion mutant. Taken together, we demonstrate that much of the projections of NEUROD1-deprived inner ear sensory neurons are regulated cell-autonomously.
Keywords: Axon guidance; Central projections; Ear neurosensory development; Neuronal differentiation; bHLH genes.
Details
- Title: Subtitle
- Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers
- Creators
- Iva FilovaMartina DvorakovaRomana BohuslavovaAdam PavlinekKaren L ElliottSimona VochyanovaBernd FritzschGabriela Pavlinkova
- Resource Type
- Journal article
- Publication Details
- Molecular neurobiology, Vol.57(12), pp.5307-5323
- DOI
- 10.1007/s12035-020-02092-0
- PMID
- 32880858
- PMCID
- PMC7547283
- NLM abbreviation
- Mol Neurobiol
- ISSN
- 0893-7648
- eISSN
- 1559-1182
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AG060504; DOI: 10.13039/501100001824, name: Grantová Agentura České Republiky, award: 20-06927S; DOI: 10.13039/501100004240, name: Akademie Věd České Republiky, award: RVO: 86652036
- Language
- English
- Date published
- 09/03/2020
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070415102771
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