Molecular specializations underlying phenotypic differences in inner ear hair cells of zebrafish and mice

Kimberlee P Giffen; Huizhan Liu; Kacey L Yamane; Yi Li; Lei Chen; Kenneth L Kramer; Marisa Zallocchi; David Z He

doi:10.3389/fneur.2024.1437558

Molecular specializations underlying phenotypic differences in inner ear hair cells of zebrafish and mice

Front Neurol. 2024 Oct 17:15:1437558. doi: 10.3389/fneur.2024.1437558. eCollection 2024.

Authors

Kimberlee P Giffen^{1

2

3}, Huizhan Liu³, Kacey L Yamane³, Yi Li^{3

4}, Lei Chen⁵, Kenneth L Kramer³, Marisa Zallocchi³, David Z He³

Affiliations

¹ Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, United States.
² Department of Basic Sciences, Augusta University/University of Georgia Medical Partnership, Athens, GA, United States.
³ Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, United States.
⁴ Department of Otorhinolaryngology, Beijing Tongren Hospital, Beijing Capital Medical University, Beijing, China.
⁵ Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States.

Abstract

Introduction: Hair 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 HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs).

Methods: To understand the genetic mechanisms underlying differences between adult zebrafish and mammalian HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization.

Results: There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. 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. For example, OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of slc26a5, 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.

Discussion: 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.

Keywords: RNA-seq; gene orthologs; hair cells; hearing; mouse; prestin; transcriptome; zebrafish.

Abstract

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