Sandler Jeremy E, Tsai Ya-Yin, Chen Shiyuan, Sabin Logan, Lush Mark E, Sur Abhinav, Ellis Elizabeth, Tran Nhung T T, Cook Malcolm, Scott Allison R, Kniss Jonathan S, Farrell Jeffrey A, Piotrowski Tatjana
Stowers Institute for Medical Research, Kansas City, MO, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
Nat Commun. 2025 Aug 18;16(1):7662. doi: 10.1038/s41467-025-62942-0.
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.
脊椎动物的内耳机械感觉毛细胞能检测声音和重力。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脊椎动物的侧线和耳朵中的毛细胞在受损后很容易再生,但哺乳动物缺乏这种能力,这会导致耳聋和前庭缺陷。到目前为止,在小鼠中进行毛细胞再生的实验尝试产生的是未完全分化和不成熟的毛细胞。尽管再生能力存在差异,但在发育过程中驱动毛细胞成熟的基因调控网络(GRN)在整个脊椎动物中高度相似。在这里,我们表明转录因子prdm1a在斑马鱼侧线的毛细胞命运GRN中起关键作用。使prdm1a发生突变会将侧线毛细胞重新指定为耳毛细胞,从而改变形态和转录组。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。
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