Helios is a key transcriptional regulator of outer hair cell maturation. (29th November 2018) - Chessum, Lauren
Abstract The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1 . Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identifyIkzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in thecello mouse model a point mutation inIkzf2 causes early-onset sensorineural hearing loss.Ikzf2 cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such asSlc26a5 (which encodes prestin) andOcm . Moreover, we show that ectopic expression ofIkzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating thatIkzf2 can partially shift the IHC transcriptome towards an OHC-like identity. Ikzf2, which encodes the transcription factor Helios, is identified as a crucial regulator of gene expression in maturing cochlear outer hair cells, and overexpression ofIkzf2 in inner hair cells induces prestin expression and electromotility.