prdm1a is at the Core of Lateral Line Sensory Hair Cell Developmental and Evolutionary Gene Regulatory Networks

In vertebrates, mechanosensory hair cells (HCs) in the ear transduce vibrations into sound. Aquatic vertebrates possess exterior lateral line HCs to detect water vibrations to orient themselves and for predator avoidance. HCs in many species regenerate following death, but mammalian HCs lack this ability, causing hearing/vestibular defects. Experimentally-induced regeneration in mice results in incomplete differentiation of immature HCs. Here, we show that the transcription factor prdm1a controls the lateral line HC network in zebrafish. Loss of prdm1a results in a significant loss of hair cells and causes proliferation and regeneration defects. scRNA-seq and ATAC-seq demonstrate a HC fate switch, and ectopically expressing prdm1a and cloning and mutating enhancers demonstrates direct interaction between prdm1a and putative target genes behind the altered cell fate. Therefore, prdm1a is an ideal gene for investigating the network needed to correctly differentiate a functioning HC, a major unmet milestone in restoring hearing. Overall design: Two conditions: prdm1a mutant and homeostasis control. Three independent biological replicates per condition.