Cellular distribution of the Fragile X mental retardation protein in the inner ear: a developmental and comparative study in the mouse, rat, gerbil, and chicken

The Fragile X mental retardation protein (FMRP) is an mRNA binding protein that is essential for neural circuit assembly and synaptic plasticity. Loss of functional FMRP leads to Fragile X syndrome (FXS), a neurodevelopmental disorder characterized by sensory dysfunction including abnormal auditory processing. While the central mechanisms of FMRP regulation have been studied in the brain, whether FMRP is expressed in the auditory periphery and how it develops and functions remains unknown. In this study, we characterized the spatiotemporal distribution pattern of FMRP immunoreactivity in the inner ear of mice, rats, gerbils, and chickens. Across species, FMRP was expressed in hair cells and supporting cells, with a particularly high level in immature hair cells during the prehearing period. Interestingly, the distribution of cytoplasmic FMRP displayed an age-dependent translocation in hair cells, and this feature was conserved across species. In the auditory ganglion (AG), FMRP immunoreactivity was detected in neuronal cell bodies as well as their peripheral and central processes. Distinct from hair cells, FMRP intensity in AG neurons was high both during development and after maturation. Additionally, FMRP was evident in mature glial cells surrounding AG neurons. Together, these observations demonstrate distinct developmental trajectories across cell types in the auditory periphery. Given the importance of peripheral inputs to the maturation of auditory circuits, these findings implicate involvement of FMRP in inner ear development as well as a potential contribution of periphery FMRP to the generation of auditory dysfunction in FXS.

Automated summary

In this study, the researchers investigated the distribution and expression of FMRP in the inner ear of mice, rats, gerbils, and chickens. They found that FMRP was present in hair cells, supporting cells, and auditory ganglion neurons. The distribution of FMRP in hair cells showed age-dependent translocation, while FMRP in auditory ganglion neurons exhibited high intensity during both development and maturation. These findings suggest the involvement of FMRP in inner ear development and its potential contribution to auditory dysfunction in Fragile X syndrome.