Characterization of spatial and temporal development of Type I and Type II hair cells in the mouse utricle using new cell-type-specific markers.

Stephen Mcinturff,Joseph C Burns,Matthew W Kelley

doi:10.1242/bio.038083

Stephen Mcinturff, Joseph C Burns + Show 1 more

Open Access

https://doi.org/10.1242/bio.038083

Copy DOI

Abstract

ABSTRACTThe utricle of the inner ear, a vestibular sensory structure that mediates perception of linear acceleration, is comprised of two morphologically and physiologically distinct types of mechanosensory hair cells, referred to as Type Is and Type IIs. While these cell types are easily discriminated in an adult utricle, understanding their development has been hampered by a lack of molecular markers that can be used to identify each cell type prior to maturity. Therefore, we collected single hair cells at three different ages and used single cell RNAseq to characterize the transcriptomes of those cells. Analysis of differential gene expression identified Spp1 as a specific marker for Type I hair cells and Mapt and Anxa4 as specific markers for Type II hair cells. Antibody labeling confirmed the specificity of these markers which were then used to examine the temporal and spatial development of utricular hair cells. While Type I hair cells develop in a gradient that extends across the utricle from posterior-medial to anterior-lateral, Type II hair cells initially develop in the central striolar region and then extend uniformly towards the periphery. Finally, by combining these markers with genetic fate mapping, we demonstrate that over 98% of all Type I hair cells develop prior to birth while over 98% of Type II hair cells develop post-natally. These results are consistent with previous findings suggesting that Type I hair cells develop first and refute the hypothesis that Type II hair cells represent a transitional form between immature and Type I hair cells.

Highlights

Within the vertebrate inner ear, vestibular sensory structures are stimulated by changes in acceleration or angular velocity facilitating the perception of head position or movement (Burns and Stone, 2017)
A crescent-shaped striolar region containing a high density of Type I hair cells (HCs) is located near the center of the epithelium (Li et al, 2008; Desai et al, 2005) (Fig. 1B)
There is a greater density of Type I HCs compared to Type II HCs in the extrastriola, the ratio is slightly less than in the striola

Summary

Introduction

Within the vertebrate inner ear, vestibular sensory structures are stimulated by changes in acceleration or angular velocity facilitating the perception of head position or movement (Burns and Stone, 2017). The two otolithic sensory patches, the utricular and saccular maculae, mediate the perception of linear acceleration while the cristae associated with each of the three semi-circular canals detect angular motion. Even within a single epithelium, HCs can be divided into Type I or Type II based on morphology, physiology and innervation (Deans, 2013; Eatock et al, 1998). There are differences in morphology; Type I HCs are generally flask-shaped with a narrow neck while Type II HCs are more cylindrical (Fig. 1A). Despite clear differences in phenotype and function, our understanding of the development of vestibular HC types, including timing and specification remains limited

Methods

Results

Conclusion