prdm1a drives a fate switch between hair cells of different mechanosensory organs
Jeremy E. SandleriD, Ya-Yin TsaiiD, Shiyuan CheniD, Logan Sabin, Mark E. LushiD, Abhinav SuriD, Elizabeth Ellis, Nhung T. T. TraniD, Malcolm E. CookiD, Allison R. ScottiD, Jonathan S. KnissiD, Jeffrey A. FarrelliD, Tatjana PiotrowskiiD
Abstract
Vertebrate mechanosensory hair cells (HCs) in the ear detect sound and gravitational forces. Additionally, fish have homologous lateral line HCs in the skin that detect water vibrations for orientation and predator avoidance. HCs in fish and other non-mammalian vertebrates regenerate to restore function after damage, but mammalian HCs lack this ability, causing deafness and vestibular defects. Experimental attempts at regeneration in mice result in incomplete differentiation of immature HCs. Despite differences in regeneration, the gene regulatory networks (GRNs) driving HC maturation are highly similar across vertebrates. Here, we show that the transcription factor prdm1a plays a key role in the HC fate GRN in the zebrafish lateral line. Mutating prdm1a respecifies lateral line HCs into ear HCs, altering morphology and transcriptome. Understanding how transcription factors control diverse HC fates in zebrafish is crucial for understanding the yet unsolved regeneration of diverse HCs in mammalian ears to restore hearing and balance.
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