Format

Send to

Choose Destination
Nature. 2018 Nov;563(7733):696-700. doi: 10.1038/s41586-018-0728-4. Epub 2018 Nov 21.

Helios is a key transcriptional regulator of outer hair cell maturation.

Author information

1
Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire, UK.
2
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
3
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
4
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
5
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
6
Mary Lyon Centre, MRC Harwell Institute, Oxfordshire, UK.
7
Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.
8
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
9
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
10
Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire, UK. m.bowl@har.mrc.ac.uk.
11
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. rhertzano@som.umaryland.edu.
12
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. rhertzano@som.umaryland.edu.
13
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA. rhertzano@som.umaryland.edu.

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 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.

PMID:
30464345
PMCID:
PMC6542691
DOI:
10.1038/s41586-018-0728-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center