Ikzf2/helios is a key transcriptional regulator of outer hair cell maturation

The sensory cells responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with OHCs being necessary for sound sensitivity and tuning. Both cell types are thought to arise from common progenitors, however our understanding of the factors that control IHC and OHC fate remains limited. Here we identify Ikzf2/helios as an essential transcription factor required for OHC functional maturation and hearing. Ikzf2/helios is expressed in postnatal mouse OHCs, and a mutation in Ikzf2 causes early-onset sensorineural hearing loss in the cello mouse model. Ikzf2(cello/cello) OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of critical OHC-expressed genes such as Slc26a5/prestin and Ocm. Moreover, we show that ectopic expression of Ikzf2/helios in IHCs induces expression of OHC-specific genes, reduces canonical IHC genes, and confers electromotility to IHCs, demonstrating that Ikzf2/helios is capable of partially shifting the IHC transcriptome towards an OHC-like identity.