Developmental Differentiation of Mouse Inner Ear Neuron Subpopulations Resolved With a Peripherin-Promoter Reporter Within the Grm8 Locus

Authors

Lily J Pearson
Jeremy L Pinyon
Jennie M E Cederholm
Georg von Jonquieres
Florence Bartlett
Xabier Vázquez-Campos
Fabien Delerue
Lars M Ittner
Gary D Housley

Publication Date

3-25-2025

Journal

Scientific Reports

Abstract

Molecular profiling of inner ear neurons has broadened the classification of the primary afferents that support neural coding for hearing and balance. To extend spatiotemporal characterization of auditory and vestibular neuron diversity, we established a transgenic reporter mouse model (Prphp-mCherry), where elements of the peripherin promoter (Prphp) drive expression of the mCherry fluorescent reporter. Type III intermediate filament protein peripherin expression is a marker for type II spiral ganglion neurons (SGN) that innervate the cochlear outer hair cells, and the small diameter 'bouton' vestibular ganglion neurons (VGN) innervating the type II vestibular hair cells. Using Nanopore genome sequencing, the integration site of the transgene construct was identified within the class III metabotropic glutamate receptor 8 gene (Grm8, chromosome 6). Use of CUBIC / PEGASOS clearing of early postnatal to adult inner ear tissues enabled in situ 3D spatial localization of a dispersed population of cochlear mCherry + ve SGN, with highest expression and density in the hook (high frequency encoding) basal region. Of these mCherry + ve SGN, type II SGN (peripherin-immunopositive) were all co-labeled in the basal region, but the majority of the overall mCherry-delineated SGN auditory subpopulation were type I SGN innervating inner hair cells. In the VGN, mCherry + ve neurons represented ~ 15% of the adult population, dispersed as a small diameter subpopulation throughout both the inferior and superior VGN regions. These findings resolve heterogeneous type I and type II cochlear SGN subpopulations, particularly in the structurally complex hook region, and further differentiate vestibular primary afferents across postnatal development.

Keywords

Animals, Mice, Promoter Regions, Genetic, Peripherins, Mice, Transgenic, Ear, Inner, Spiral Ganglion, Receptors, Metabotropic Glutamate, Cell Differentiation, Genes, Reporter, Neurons, Red Fluorescent Protein

DOI

10.1038/s41598-025-94011-3

PMID

40133378

PMCID

PMC11937576

PubMedCentral® Posted Date

3-25-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes