prdm1a drives a fate switch between hair cells of different mechanosensory organs

Jeremy E. Sandler, Ya-Yin Tsai, Shiyuan Chen, Logan Sabin, Mark E. Lush, Abhinav Sur, Elizabeth Ellis, Nhung T. T. Tran, Malcolm Cook, Allison R. Scott, Jonathan S. Kniss, Jeffrey A. Farrell and Tatjana Piotrowski ()
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Jeremy E. Sandler: Stowers Institute for Medical Research
Ya-Yin Tsai: Stowers Institute for Medical Research
Shiyuan Chen: Stowers Institute for Medical Research
Logan Sabin: Stowers Institute for Medical Research
Mark E. Lush: Stowers Institute for Medical Research
Abhinav Sur: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Elizabeth Ellis: Stowers Institute for Medical Research
Nhung T. T. Tran: Stowers Institute for Medical Research
Malcolm Cook: Stowers Institute for Medical Research
Allison R. Scott: Stowers Institute for Medical Research
Jonathan S. Kniss: Stowers Institute for Medical Research
Jeffrey A. Farrell: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Tatjana Piotrowski: Stowers Institute for Medical Research

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-62942-0

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