Abstract:
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.
摘要:
脊椎动物内耳的机械感觉毛细胞对听觉或重力加速度变化引起的机械偏转做出反应,让我们感知和解释声音,保持平衡和空间取向。在哺乳动物中,耳毒性化合物,疾病,和声学创伤会导致毛细胞的损伤和挤压,没有替换,导致听力损失。相比之下,非哺乳动物脊椎动物可以再生感觉毛细胞。一旦损坏,毛细胞被挤压和相关的细胞类型,支持细胞转化为毛细胞。可以触发再生的机制是未知的。利用毛细胞主基因的马赛克缺失,Atoh1,在鸟类的胚胎内耳,我们发现,尽管毛细胞在E9时耗尽,到E12时,毛细胞数量在感觉上皮中恢复。我们的研究表明,稳态机制可以恢复基底乳头中的毛细胞数量,当juxrine信号中断时被激活。在发育过程中恢复毛细胞数量可能反映再生过程,我们的工作提供了触发再生的机制的见解。