Helios is a key transcriptional regulator of outer hair cell maturation

Lauren Chessum, Maggie S. Matern, Michael C. Kelly, Stuart L. Johnson, Yoko Ogawa, Beatrice Milon, Mark McMurray, Elizabeth C. Driver, Andrew Parker, Yang Song, Gemma Codner, Christopher T. Esapa, Jack Prescott, Graham Trent, Sara Wells, Abigail K. Dragich, Gregory I. Frolenkov, Matthew W. Kelley, Walter Marcotti, Steve D.M. BrownRan Elkon, Michael R. Bowl*, Ronna Hertzano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 identify Ikzf2 (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 the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/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 as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.

Original languageEnglish
Pages (from-to)696-724
Number of pages29
Issue number7733
StatePublished - 2018


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