Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear

Gabriela Pavlinkova; Pin-Xian Xu; Kathryn S E Cheah; Ebenezer N Yamoah; Bernd Fritzsch

doi:10.1007/s10162-025-01024-w

Back

Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear

Journal article

Open access

Peer reviewed

Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear

Gabriela Pavlinkova, Pin-Xian Xu, Kathryn S E Cheah, Ebenezer N Yamoah and Bernd Fritzsch

Journal of the Association for Research in Otolaryngology, Vol.27(1), pp.5-24

02/2026

DOI: 10.1007/s10162-025-01024-w

PMID: 41491447

Files and links (1)

url

https://doi.org/10.1007/s10162-025-01024-wView

Published (Version of record) Open Access

Abstract

Vestibular and spiral ganglion neurons (VGNs and SGNs) developed in the inner ear, where they extend fibers to innervate the vestibular and cochlear hair cells and project centrally to the vestibular and cochlear nuclei. This review focuses on representative molecular factors that regulate key processes in the development of inner ear neurons, including their specification, differentiation, axon targeting, and functional diversification. A temporal regulatory cascade defines the initial precursors through factors such as Smarca4, Six1, Eya1, followed by Sox2. While Sox2 deletion abolishes hair cell formation, a subset of inner ear neurons transiently develops but undergoes apoptosis before birth. In contrast, Neurog1 deletion eliminates all ear-derived neurons but results in differential reductions in cochlear and vestibular hair cells. The development and survival of inner ear neurons depend on TrkB and TrkC signaling. Although deletion of TrkB and TrkC results in a complete loss of neurons, each shows distinct effects on VGN and SGN survival and innervation. Downstream of early transcriptional regulators, Neurod1 and Isl1 promote neuronal differentiation, survival, migration, and the formation of peripheral and central projections. The development of VGNs depends on at least two progenitor populations that give rise to three neuronal subtypes that differ in their innervation of vestibular hair cells but show incomplete segregation in the vestibular nuclei. In contrast, SGNs develop later and exhibit sequential segregation into four neuronal subtypes, corresponding to the two types of cochlear hair cells, with tonotopically organized projections to both the cochlea and cochlear nuclei.

Neurogenesis

Development

Projections

Vestibular neurons

Cochlear neurons

Details

Title: Subtitle: Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear
Creators: Gabriela Pavlinkova - Czech Academy of Sciences, Institute of Molecular Genetics
Pin-Xian Xu - Icahn School of Medicine at Mount Sinai
Kathryn S E Cheah - Chinese University of Hong Kong
Ebenezer N Yamoah - University of Arizona
Bernd Fritzsch - University of Nebraska Medical Center
Resource Type: Journal article
Publication Details: Journal of the Association for Research in Otolaryngology, Vol.27(1), pp.5-24
DOI: 10.1007/s10162-025-01024-w
PMID: 41491447
NLM abbreviation: J Assoc Res Otolaryngol
ISSN: 1438-7573
eISSN: 1438-7573
Publisher: Springer
Grant note: AG051443 / NIH HHS
Language: English
Electronic publication date: 01/05/2026
Date published: 02/2026
Academic Unit: Biology; Craniofacial Anomalies Research Center
Record Identifier: 9985114162902771

Metrics

9 Record Views