Biology subjects

Kulasooriya, S.

Publications and source records attributed to Kulasooriya, S..

2 recordsLinked to original sources

bioRxiv2025

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

Vestibular hair cells (HCs) convert gravitational and head motion cues into neural signals through mechanotransduction, mediated by the hair bundle--a mechanically integrated organelle composed of stereocilia and a kinocilium. The kinocilium, a specialized form of primary cilium, remains incompletely defined in structure, molecular composition, and function. To elucidate its characteristics, we conducted single-cell RNA sequencing of adult vestibular and cochlear HCs, uncovering a selective enrichment of primary and motile cilia-associated genes in vestibular HCs, particularly those related to the axonemal repeat complex. This enrichment of orthologous axonemal-related genes was conserved in zebrafish and human vestibular HCs, indicating a shared molecular architecture. Immunostaining validated the expression of key motile cilia markers in vestibular kinocilia. Moreover, live imaging of bullfrog and mouse HCs from crista ampullaris revealed spontaneous kinociliary motion. Together, these findings define the kinocilium as a unique organelle with molecular features of primary and motile cilia and suggest its previously unknown role as an active, force-generating element within the hair bundle.

neuroscience↗

bioRxiv2025

Single-cell Transcriptomics Unravel Stereocilia Degeneration as a Key Contributor to Age-related Vestibular Dysfunction in Mice and Humans

Age-related vestibular dysfunction (ARVD) is a prevalent, debilitating condition in the elderly. The etiology and molecular mechanisms are poorly understood. We focused on mechanosensitive hair cells (HCs) as they are vulnerable to aging. Using single-cell RNA-seq transcriptomes of young and old mouse vestibular HCs, we show that aging vestibular HCs display both universal molecular signatures, such as genomic instability, mitochondrial dysfunction, and impaired proteostasis, and cell type-specific changes associated with deterioration of hair bundles and mechanotransduction. In alignment with transcriptomic findings, imaging and electrophysiological recordings from aged vestibular sensory epithelia confirmed the degeneration of the hair bundles and a reduction in mechanotransduction. Importantly, this deterioration of hair bundles and vestibular function precedes HC loss, highlighting impaired mechanotransduction as a key contributor to ARVD. Furthermore, molecular and cellular changes associated with aging signatures are less pronounced in vestibular HCs than in cochlear HCs, underscoring tissue-specific age-related differences between the two sensory epithelia in the inner ear.

neuroscience↗