Development in the Mammalian Auditory System Depends on Transcription Factors

Karen L Elliott; Gabriela Pavlínková; Victor V Chizhikov; Ebenezer N Yamoah; Bernd Fritzsch

doi:10.3390/ijms22084189

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Development in the Mammalian Auditory System Depends on Transcription Factors

Journal article

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Development in the Mammalian Auditory System Depends on Transcription Factors

Karen L Elliott, Gabriela Pavlínková, Victor V Chizhikov, Ebenezer N Yamoah and Bernd Fritzsch

International journal of molecular sciences, Vol.22(8), p.4189

04/18/2021

DOI: 10.3390/ijms22084189

PMID: 33919542

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Abstract

We review the molecular basis of several transcription factors ( Eya1 , Sox2 ), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins ( Neurog1 , Neurod1 , Atoh1 ) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstream target Neurod1 , to cross-regulate Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 expression for interactions with Atoh1 . Upregulation of Atoh1 following Neurod1 loss changes some vestibular neurons’ fate into “hair cells”, highlighting the significant interplay between the bHLH genes. Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. The inhibition of Atoh1 by Neurod1 is essential for proper neuronal cell fate, and in the absence of Neurod1 , Atoh1 is upregulated, resulting in the formation of “intraganglionic” HCs. Additional genes, such as Eya1/Six1 , Sox2, Pax2, Gata3, Fgfr2b, Foxg1 , and Lmx1a/b , play a role in the auditory system. Finally, both Lmx1a and Lmx1b genes are essential for the cochlear organ of Corti, spiral ganglion neuron, and cochlear nuclei formation. We integrate the mammalian auditory system development to provide comprehensive insights beyond the limited perception driven by singular investigations of cochlear neurons, cochlear hair cells, and cochlear nuclei. A detailed analysis of gene expression is needed to understand better how upstream regulators facilitate gene interactions and mammalian auditory system development.

transcription factors

cochlea hair cells

spiral ganglion neurons

cochlear nuclei

Review

bHLH genes

neuronal differentiation

Details

Title: Subtitle: Development in the Mammalian Auditory System Depends on Transcription Factors
Creators: Karen L Elliott - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Gabriela Pavlínková - Institute of Biotechnology of the Czech Academy of Sciences, 25250 Vestec, Czechia
Victor V Chizhikov - Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
Ebenezer N Yamoah - Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA
Bernd Fritzsch - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.22(8), p.4189
DOI: 10.3390/ijms22084189
PMID: 33919542
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Publisher: MDPI
Grant note: name: National Institute for Aging, award: R01 AG060504
Language: English
Date published: 04/18/2021
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070992002771

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