Molecular Specializations Underlying Phenotypic Differences in Inner Ear Hair Cells of Zebrafish and Mice

Abstract

AbstractHair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian cochlear HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). To understand the genetic mechanisms underlying differences among adult zebrafish and mammalian cochlear HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. For example, both zebrafish and mouse HCs expressTmc1, Lhfpl5, Tmie, Cib2, Cacna1d, Cacnb2, Otof, PcloandSlc17a8. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type.Tmc2 and Cib3were not detected in adult mouse HCs buttmc2aandbandcib3were highly expressed in zHCs. Mouse HCs expressKcna10,Kcnj13,Kcnj16, andKcnq4, which were not detected in zHCs.Chrna9andChrna10were expressed in mouse HCs. In contrast,chrna10was not detected in zHCs. OHCs highly expressSlc26a5which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression ofslc26a5, and subsequently showed no voltage dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.