Sandler Jeremy E, Tsai Ya-Yin, Chen Shiyuan, Sabin Logan, Lush Mark E, Sur Abhinav, Ellis Elizabeth, Tran Nhung Tt, Cook Malcolm, Scott Allison R, Kniss Jonathan S, Farrell Jeffrey A, Piotrowski Tatjana
Stowers Institute for Medical Research, Kansas City, Missouri, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
bioRxiv. 2025 Jun 3:2025.06.01.657251. doi: 10.1101/2025.06.01.657251.
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 plays a key role in the HC fate GRN in the zebrafish lateral line. Mutating 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.
耳朵中的脊椎动物机械感觉毛细胞（HCs）能检测声音和重力。此外，鱼类在皮肤中有同源的侧线毛细胞，可检测水的振动以进行定向和躲避捕食者。鱼类和其他非哺乳动物的脊椎动物中的毛细胞在受损后会再生以恢复功能，但哺乳动物的毛细胞缺乏这种能力，会导致耳聋和前庭缺陷。在小鼠中进行再生的实验尝试导致未成熟毛细胞的不完全分化。尽管在再生方面存在差异，但驱动毛细胞成熟的基因调控网络（GRNs）在整个脊椎动物中高度相似。在这里，我们表明转录因子在斑马鱼侧线的毛细胞命运基因调控网络中起关键作用。使 突变会将侧线毛细胞重新指定为耳毛细胞，改变形态和转录组。了解转录因子如何控制斑马鱼中不同的毛细胞命运对于理解哺乳动物耳朵中尚未解决的各种毛细胞再生以恢复听力和平衡至关重要。
