National Centre for Biological Sciences, Tata Institute for Fundamental Research, GKVK PO, Bellary Road, Bangalore, 560065, India; The University of Trans-Disciplinary Health Sciences and Technology, Yelahanka, Bangalore, 560064, India.
National Centre for Biological Sciences, Tata Institute for Fundamental Research, GKVK PO, Bellary Road, Bangalore, 560065, India.
Dev Biol. 2024 Dec;516:35-46. doi: 10.1016/j.ydbio.2024.07.017. Epub 2024 Jul 27.
The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.
脊椎动物内耳的机械感觉毛细胞对听觉引起的机械偏转而产生反应，或者对由于重力变化而产生的加速度做出反应，从而使我们能够感知和解释声音，保持平衡和空间定向。在哺乳动物中，耳毒性化合物、疾病和声音创伤会导致毛细胞受损和挤出，而没有替代物，从而导致听力损失。相比之下，非哺乳动物的脊椎动物可以再生感觉毛细胞。在受损后，毛细胞被挤出，一个相关的细胞类型，支持细胞，转变成毛细胞。可以触发再生的机制尚不清楚。通过在胚胎鸡内耳中对毛细胞主基因 Atoh1 进行镶嵌缺失，我们发现尽管在 E9 时耗尽了毛细胞，但到 E12 时，感觉上皮中的毛细胞数量得到了恢复。我们的研究表明，一种平衡机制可以恢复基底乳头中的毛细胞数量，这种机制在旁分泌信号受到干扰时被激活。在发育过程中恢复毛细胞数量可能反映了再生过程，我们的工作为触发再生的机制提供了深入的了解。
