Mechanotransduction-dependent control of stereocilia dimensions and row identity in inner hair cells

Summary Actin-rich structures like stereocilia and microvilli are assembled with precise control of length, diameter, and relative spacing. We found that developmental widening of the second-tallest stereocilia rank (row 2) of mouse inner hair cells correlated with the appearance of mechanotransduction. Correspondingly, Tmc1KO/KO;Tmc2KO/KO or TmieKO/KO hair cells, which lack transduction, have significantly altered stereocilia lengths and diameters. EPS8 and the short splice isoform of MYO15A, identity markers for row 1 (tallest), lost their row exclusivity in transduction mutants, a result that was mimicked by block of transduction channels. Likewise, the heterodimeric capping protein subunit CAPZB and its partner TWF2 lost their row 2 tip localization in mutants, and GNAI3 failed to accumulate at row 1 tips. Redistribution of marker proteins was accompanied by increased variability in stereocilia height. Transduction channels thus specify and maintain row identity and control addition of new actin filaments to increase stereocilia diameter.