FCHSD2 is required for stereocilia maintenance in mouse cochlear hair cells.

Stereocilia are F-actin-based protrusions on the apical surface of inner-ear hair cells and are indispensable for hearing and balance perception. The stereocilia of each hair cell are organized into rows of increasing heights, forming a staircase-like pattern. The development and maintenance of stereocilia are tightly regulated, and deficits in these processes lead to stereocilia disorganization and hearing loss. Previously, we showed that the F-BAR protein FCHSD2 is localized along the stereocilia of cochlear hair cells and cooperates with CDC42 to regulate F-actin polymerization and cell protrusion formation in cultured COS-7 cells. In the present work, Fchsd2 knockout mice were established to investigate the role of FCHSD2 in hearing. Our data show that stereocilia maintenance is severely affected in cochlear hair cells of Fchsd2 knockout mice, which leads to progressive hearing loss. Moreover, Fchsd2 knockout mice show increased acoustic vulnerability. Noise exposure causes robust stereocilia degeneration as well as enhanced hearing threshold elevation in Fchsd2 knockout mice. Lastly, Fchsd2/Cdc42 double knockout mice show more severe stereocilia deficits and hearing loss, suggesting that FCHSD2 and CDC42 cooperatively regulate stereocilia maintenance.