Fibroblast growth factor 12 is expressed in spiral and vestibular ganglia and necessary for auditory and equilibrium function

Abstract

We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.

Genetic Adaptation in New York City Rats

“…CACNA1C and multiple other top-scoring genes like FGF12, EPHA3, and CHAT ( supplementary table S4 , Supplementary Material online) may also affect locomotion in rodents ( Wurzman et al. 2015 ; Hanada et al. 2018 ).…”

Genetic Adaptation in New York City Rats

“…CACNA1C has also been demonstrated to influence social behavior and communication in rats [55]. CACNA1C and multiple other top-scoring genes like FGF12, EPHA3 and CHAT ( Table S4 ) may also affect locomotion in rodents [56, 57]. The gait or other locomotory phenotypes could have also undergone adaptive changes, given that urban rats must move through a highly artificial, constructed environment that differs markedly from naturally vegetated habitats.…”

Cochlear protection against noise exposure requires serotonin type 3A receptor via the medial olivocochlear system

“…We used alternating polarity click stimuli of 100 µs in duration, 8 and 16 kHz tones, and bursts with a 0.1‐ms linear rise and fall envelope. The duration of the tone bursts was 1 ms An algorithm for automated determination of the ABR amplitudes, which was based on the definitions provided above, was developed by the Bio Research Center (Nagoya, Japan) 20 . Thresholds were determined in 5‐dB steps of decreasing stimulus intensity until waveforms had lost reproducible morphologies (from 80 dB to below 5 dB of SPL).…”

“…Isolated cochleas were postfixed in 4% paraformaldehyde in 0.1-M phosphate-buffered saline (PBS) for 2 hours and then decalcified in 10% EDTA for 4 days. 20 The basilar membrane containing the organ of Corti was microdissected and divided into three regions: basal, middle, and apical. 25 Microdissected pieces were immunostained with antibodies against GFP (chicken; Abcam, UK; 1:1000; Cat# ab13970, RRID: AB_300798) and choline acetyltransferase (ChAT) (goat; Merck Millipore, USA; 1:200; Cat# AB144P, RRID: AB_2079751).…”

“…Isolated cochleas were postfixed in 4% paraformaldehyde in 0.1-M PBS for 2 hours and then decalcified in 10% EDTA for 4 days. 20 Microdissected pieces of the cochlear were immunostained with anti-CtBP2 (mouse; BD Biosciences, USA; 1:200; Cat# 612 044, RRID: AB_399431) and anti-GluA2 (mouse, Millipore; 1:2000; Cat# MAB397, RRID: AB_2113875) antibodies and the appropriate secondary antibodies. Images of surface preparations were acquired under the LSM 880 confocal laser scanning microscope.…”