"Transcription Co-Factor LBH Is Necessary for Maintenance of Stereocilia Bundles and Survival of Cochlear Hair Cells"

Inner hair cells (IHCs) and outer hair cells (OHCs) are the two types of sensory receptor cells critical for hearing in the mammalian cochlea. Although both types of hair cells have the hallmark of stereocilia bundle in their apical surface, IHCs and OHCs have different morphology and function. The molecular mechanisms that control their differentiation, maturation and homeostasis are largely unknown. Lbh, encoding LBH, a transcription co-factor important for development of the limb bud and heart, is expressed in both IHCs and OHCs with preferential expression in OHCs. In the present study we examined the role of LBH by comparing changes in hair cell morphology and function between Lbh knockout and wild-type mice. Nascent IHCs and OHCs had normal looking stereocilia bundle when examined under scanning electron microscopy. Whole-cell recording showed that the stereocilia bundle was mechanosensitive and OHCs exhibited the characteristic electromotility. However, stereocilia and hair cells, especially OHCs, degenerated after hearing onset, which leads to progressive loss of hearing and otoacoustic emissions from high to low frequencies. Cell-specific RNA-seq and bioinformatic analyses identified significant gene enrichment in Lbh-null OHCs associated with biological processes including transcription, cell cycle, Wnt signaling and Notch signaling. Our study suggests that LHB is not critical for hair cell differentiation, but essential for their survival.