prdm1a drives a fate switch between hair cells of different mechanosensory organs
Vertebrate inner ear mechanosensory hair cells detect sound and gravitational forces. Additionally, fishes have homologous lateral line hair cells in the skin that detect water vibrations for orientation and predator avoidance. Hair cells in the lateral line and ear of fishes and other non-mammalian vertebrates regenerate readily after damage, but mammalians lack this ability, causing deafness and vestibular defects. As yet, experimental attempts at hair cell regeneration in mice result in incompletely differentiated and immature hair cells. Despite differences in regeneration capabilities, the gene regulatory networks (GRNs) driving hair cell maturation during development are highly similar across vertebrates. Here, we show that the transcription factor prdm1a plays a key role in the hair cell fate GRN in the zebrafish lateral line. Mutating prdm1a respecifies lateral line hair cells into ear hair cells, altering morphology and transcriptome. Understanding how transcription factors control diverse hair cell fates in zebrafish is crucial for understanding the yet unsolved regeneration of diverse hair cells in mammalian ears to restore hearing and balance.
Authors
- Jonathan S. Kniss (ORCID: https://orcid.org/0009-0000-9223-2092)
- Abhinav Sur (ORCID: https://orcid.org/0000-0003-2236-1459)
- Nhung T. T. Tran (ORCID: https://orcid.org/0000-0002-9660-8904)
- Malcolm Cook (ORCID: https://orcid.org/0000-0002-2825-9183)
- Ya-Yin Tsai (ORCID: https://orcid.org/0000-0002-9152-7646)
- Tatjana Piotrowski (ORCID: https://orcid.org/0000-0001-8098-2574)
- Mark E. Lush (ORCID: https://orcid.org/0000-0002-2128-524X)
- Jeffrey A. Farrell (ORCID: https://orcid.org/0000-0003-4774-1562)
- Shiyuan Chen (ORCID: https://orcid.org/0000-0001-9805-2906)
- Jeremy E. Sandler
- E. Ellis
- Allison Scott
- Logan Sabin
Institutions
- Stowers Institute for Medical Research (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- SUNY Fredonia (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1038/s41467-025-62942-0
- Citations
- 2
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 2.93
Funders
- Hearing Health Foundation
- Stowers Institute for Medical Research
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development