Neurog1, Neurod1, and Atoh1 are essential for spiral ganglia, cochlear nuclei, and cochlear hair cell development

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

doi:10.12703/r/10-47

Neurog1, Neurod1, and Atoh1 are essential for spiral ganglia, cochlear nuclei, and cochlear hair cell development

Fac Rev. 2021 May 11:10:47. doi: 10.12703/r/10-47. eCollection 2021.

Authors

Karen L Elliott¹, Gabriela Pavlinkova², Victor V Chizhikov³, Ebenezer N Yamoah⁴, Bernd Fritzsch¹

Affiliations

¹ Department of Biology, University of Iowa, Iowa City, IA, USA.
² Institute of Biotechnology of the Czech Academy of Sciences, Vestec, Czechia.
³ Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁴ Department of Physiology and Cell Biology, University of Nevada, Reno, NV, USA.

Abstract

We review the molecular basis of three related basic helix-loop-helix (bHLH) genes (Neurog1, Neurod1, and Atoh1) and upstream regulators Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires early expression of Neurog1, followed by its downstream target Neurod1, which downregulates Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 and Neurog1 expression for various aspects of development. Several experiments show a partial uncoupling of Atoh1/Neurod1 (spiral ganglia and cochlea) and Atoh1/Neurog1/Neurod1 (cochlear nuclei). In this review, we integrate the cellular and molecular mechanisms that regulate the development of auditory system and provide novel insights into the restoration of hearing loss, beyond the limited generation of lost sensory neurons and hair cells.

Keywords: bHLH genes; cochlea development; cochlear nuclei projections; neuronal differentiation.

Publication types

Review

Grants and funding

This work was supported by National Institutes of Health/National Institute on Aging grants R01 AG060504 (KE, BF, and ENY), P01AG051443, and R01 DC016099R01 and DC05135 (ENY), the Czech Science Foundation (20-06927S) (GP), and the institutional support of the Czech Academy of Sciences RVO: 86652036 (GP).