Early Deletion of Neurod1 Alters Neuronal Lineage Potential and Diminishes Neurogenesis in the Inner Ear

Iva Filova; Romana Bohuslavova; Mitra Tavakoli; Ebenezer N. Yamoah; Bernd Fritzsch; Gabriela Pavlinkova

doi:10.3389/fcell.2022.845461

Back

Early Deletion of Neurod1 Alters Neuronal Lineage Potential and Diminishes Neurogenesis in the Inner Ear

Journal article

Open access

Peer reviewed

Early Deletion of Neurod1 Alters Neuronal Lineage Potential and Diminishes Neurogenesis in the Inner Ear

Iva Filova, Romana Bohuslavova, Mitra Tavakoli, Ebenezer N. Yamoah, Bernd Fritzsch and Gabriela Pavlinkova

Frontiers in cell and developmental biology, Vol.10, 845461

02/01/2022

DOI: 10.3389/fcell.2022.845461

PMCID: PMC8894106

PMID: 35252209

Files and links (1)

url

https://doi.org/10.3389/fcell.2022.845461View

Published (Version of record) Open Access

Abstract

Neuronal development in the inner ear is initiated by expression of the proneural basic Helix-Loop-Helix (bHLH) transcription factor Neurogenin1 that specifies neuronal precursors in the otocyst. The initial specification of the neuroblasts within the otic epithelium is followed by the expression of an additional bHLH factor, Neurod1. Although NEUROD1 is essential for inner ear neuronal development, the different aspects of the temporal and spatial requirements of NEUROD1 for the inner ear and, mainly, for auditory neuron development are not fully understood. In this study, using Foxg1Cre for the early elimination of Neurod1 in the mouse otocyst, we showed that Neurod1 deletion results in a massive reduction of differentiating neurons in the otic ganglion at E10.5, and in the diminished vestibular and rudimental spiral ganglia at E13.5. Attenuated neuronal development was associated with reduced and disorganized sensory epithelia, formation of ectopic hair cells, and the shortened cochlea in the inner ear. Central projections of inner ear neurons with conditional Neurod1 deletion are reduced, unsegregated, disorganized, and interconnecting the vestibular and auditory systems. In line with decreased afferent input from auditory neurons, the volume of cochlear nuclei was reduced by 60% in Neurod1 mutant mice. Finally, our data demonstrate that early elimination of Neurod1 affects the neuronal lineage potential and alters the generation of inner ear neurons and cochlear afferents with a profound effect on the first auditory nuclei, the cochlear nuclei.

Neurons

auditory system

cochlear nuclei

Foxg1

Neurod1

vestibular system

Details

Title: Subtitle: Early Deletion of Neurod1 Alters Neuronal Lineage Potential and Diminishes Neurogenesis in the Inner Ear
Creators: Iva Filova - Laboratory of Molecular Pathogenesis, Institute of Biotechnology CAS, Vestec, Czechia
Romana Bohuslavova - Laboratory of Molecular Pathogenesis, Institute of Biotechnology CAS, Vestec, Czechia
Mitra Tavakoli - Laboratory of Molecular Pathogenesis, Institute of Biotechnology CAS, Vestec, Czechia
Ebenezer N. Yamoah - Department of Physiology and Cell Biology, Institute for Neuroscience, University of Nevada, Reno, NV, United States
Bernd Fritzsch - Department of Biology, University of Iowa, Iowa City, IA, United States
Gabriela Pavlinkova - Laboratory of Molecular Pathogenesis, Institute of Biotechnology CAS, Vestec, Czechia
Resource Type: Journal article
Publication Details: Frontiers in cell and developmental biology, Vol.10, 845461
DOI: 10.3389/fcell.2022.845461
PMID: 35252209
PMCID: PMC8894106
NLM abbreviation: Front Cell Dev Biol
eISSN: 2296-634X
Publisher: Frontiers Media S.A
Grant note: DOI: 10.13039/501100001824, name: Grantová Agentura České Republiky; DOI: 10.13039/501100004240, name: Akademie Věd České Republiky; DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 02/01/2022
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984221660102771

Metrics

29 Record Views

21 Times Cited - Web of Science