Abstract
The middle ear conducts sound to the cochlea for hearing. Otitis media (OM) is the most common illness in childhood. Moreover, chronic OM with effusion (COME) is the leading cause of conductive hearing loss. Clinically, COME is highly associated with Primary Ciliary Dyskinesia, implicating significant contributions of cilia dysfunction to COME. The understanding of middle ear cilia properties that are critical to OM susceptibility, however, is limited. Here, we confirmed the presence of a ciliated region near the Eustachian tube orifice at the ventral region of the middle ear cavity, consisting mostly of a lumen layer of multi-ciliated and a layer of Keratin-5-positive basal cells. We also found that the motile cilia are polarized coordinately and display a planar cell polarity. Surprisingly, we also found a region of multi-ciliated cells that line the posterior dorsal pole of the middle ear cavity which was previously thought to contain only non-ciliated cells. Our study provided a more complete understanding of cilia distribution and revealed for the first time coordinated polarity of cilia in the epithelium of the mammalian middle ear, thus illustrating novel structural features that are likely critical for middle ear functions and related to OM susceptibility.
Highlights
Planar cell polarity (PCP)[26,32,33,34,35,36], which refers to the coordinated polarization of cells along the plane of the tissue
In addition to the microtubules, the basal body consists of an appendage structure, the basal foot, which marks the orientation of the cilium and is composed of specific proteins that are electron dense on transmission electron microscopy (TEM) micrographs[21,27,38,39]
We isolated temporal bones from P30-P120 mice, decalcified the samples, prepared oblique transverse cryosections of the temporal bones (Fig. 1a), and stained the sections with an antibody against acetylated α-tubulin that was enriched in cilia axoneme[44] (Figs 1b–f and 2, S1) and an antibody against Arl13b (Fig. 1g) that was localized to the cilia axoneme[45]
Summary
Planar cell polarity (PCP)[26,32,33,34,35,36], which refers to the coordinated polarization of cells along the plane of the tissue. We found a second population of ciliated cells in the epithelium lining the middle ear cavity This second population of ciliated epithelial cells cover the dorsal region of the middle ear cavity within the epithelium derived from neural crests[17]. This population of ciliated cells have the same composition of Keratin 5-posive basal cells and Keratin 5-negative multi-ciliated cells normally observed in the multi-ciliated mucosa[40,41,42,43], including the middle ear ciliated epithelium near the Eustachian tube orifice. These results provide new insights into the potential functions of cilia in the middle ear, and point to the importance of cilia and cilial polarity in both the normal functioning and pathogenesis of the middle ear
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