Hair Bundle Structure and Dynamics
EMSL Project ID
60715
Abstract
A principal long-term goal of our lab is to describe the molecular steps leading to hair-bundle assembly. As the mechanosensitive organelle of a hair cell, a bundle responds to mechanical forces by opening transduction channels and electrically exciting the cell. During development, the bundle forms by systematic and differential growth of its ~100 stereocilia, leading to its characteristic structure. Because many deafness mutations disrupt bundle development, better understanding of assembly could lead to therapeutic approaches for hearing loss. Inner hair cells (IHCs*) of the cochlea are the true sensory cells of the auditory system. Their hair bundles share key organizational features with all bundles, including the staircase-like systematic increase in stereocilia length from row to row. Nevertheless, dimensions of IHC stereocilia—their lengths, widths, and staircase spacing—are distinct from those of other hair cells, including as the nearby outer hair cells (OHCs). We hypothesize that nonuniformities in IHC bundles provide clues as to how the different rows of stereocilia form in all bundles. If so, IHCs should be an excellent model system for studying bundle assembly. Fortunately, all of the tools we use for characterizing bundles—e.g., imaging, bundle isolation, proteomics, genetics—can be applied to bundles of mouse IHCs, making them particularly suitable for comprehensive analysis.
We recently showed that like chick cochlea stereocilia, mouse IHC stereocilia grow through sequential early lengthening, widening, and late lengthening steps; notably, rows 1 and 2 differ substantially in the timing and extent of stereocilia growth. Others have shown that lengthening is controlled by an 'elongation complex', which includes MYO15A, EPS8, WHRN, GPSM2, and GNAI3. Less is known about the widening step; mouse mutants have indicated the participation of (at least) ESPN, CAPZB, and GRXCR1, and our recent results show that mechanotransduction regulates this process. In mature IHC bundles, row 1 and 2 stereocilia (the tallest) are particularly thick, which likely contributes to efficient activation of these bundles by hydrodynamic flow, the principal modality of IHC excitation. Developmental widening of stereocilia, an underappreciated process, is thus essential for proper function of the auditory system.
Project Details
Start Date
2023-04-24
End Date
N/A
Status
Active
Released Data Link
Team
Principal Investigator
Team Members