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April 21st, 2025
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Creighton University
neuroscience
biorxiv

Kinocilia of Vestibular Hair Cells: Bridging Structural and Functional Traits of Primary and Motile Cilia

Xu, Z.Open in Google Scholar•Tavakoli, A.Open in Google Scholar•Kulasooriya, S.Open in Google Scholar•Liu, H.Open in Google Scholar•Tu, S.Open in Google Scholar•Bloom, C.Open in Google Scholar•Li, Y.Open in Google Scholar•Zuo, J.Open in Google Scholar•Tao, L.Open in Google Scholar•Kachar, B.Open in Google Scholaret al.

Vestibular hair cells (HCs) detect head motion and orientation by transducing mechanical forces generated by gravity and acceleration into neural signals. This mechanotransduction is mediated by the hair bundle, which comprises stereocilia and a single kinocilium - the latter considered a specialized form of primary cilium. To investigate the characteristics of the kinocilium, we performed single-cell RNA sequencing on 1,522 adult vestibular and cochlear HCs. Our analysis revealed an enrichment of genes associated with motile cilia in vestibular HCs, particularly those linked to the axonemal repeat complex, a defining structural feature of motile cilia. Orthologous axonemal-related genes were also identified in zebrafish and human vestibular HCs, highlighting a conserved molecular architecture of kinocilia across vertebrate species. Immunostaining confirmed the expression of key motile cilia markers - including CCDC39, CCDC40, DNAH5, and DNAH6 - in vestibular kinocilia. Live imaging of bullfrog saccular and mouse crista HCs revealed spontaneous kinociliary motion that drove oscillations of the hair bundle. Together, these findings establish the kinocilium as a distinct organelle with molecular hallmarks of motile cilia and suggest it functions as an active, force-generating hair bundle component, potentially influencing the mechanosensitivity of the kinocilium-bearing HCs across nonmammalian and mammalian species.

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