Zebrafish Inner Ear Regeneration

项目摘要 内耳中的机械感觉毛细胞损失是听力和平衡障碍的主要原因。 不幸的是，头发细胞的损失是永久性的，因为人类几乎没有或没有再生恢复头发的能力。 细胞虽然最近在哺乳动物毛细胞的恢复方面取得了进展， 发育过程中使用的基因和途径的表达，功能恢复在很大程度上是不完整的， 在产后发育的有限窗口内。相比之下，从鱼类到鸟类的非哺乳动物物种 很容易从周围的支持细胞前体取代毛细胞。了解毛细胞的关键 再生是鉴定维持再生的支持细胞亚群。的 斑马鱼是一种成熟的研究再生的系统，具有先进的遗传学优势， 活体动物的活体成像。在了解再生方面已经取得了相当大的进展， 侧线系统，身体表面的一系列机械感觉毛细胞用于检测水流 与内耳的毛细胞有许多共同的特性。相比之下， 细胞再生在斑马鱼内耳，主要是因为一直没有可靠的方法， 快速和可再生的损害。此外，我们对斑马鱼内部的支持细胞类型知之甚少， 耳朵克服这两个障碍将建立斑马鱼内耳作为毛细胞的新模型 再生我们建议开发工具，在斑马鱼快速，可重复的损伤和再生 内耳我们还建议确定内耳支持细胞类型，包括潜在的毛细胞前体。 成功完成这些目标将为社区开始新的研究提供重要的工具， 斑马鱼内耳再生

PROJECT SUMMARY Mechanosensory hair cell loss in the inner ear is a leading cause of hearing and balance disorders. Unfortunately hair cell loss is permanent as humans have little or no capacity for regenerative recovery of hair cells. Although there has been recent progress in the restoration of hair cells in mammals by promoting expression of genes and pathways used during development, functional restoration is largely incomplete and within a limited window of postnatal development. By contrast non-mammalian species from fish to birds readily replace hair cells from surrounding supporting cell precursors. Critical to understanding hair cell regeneration is the identification of the subpopulations of supporting cells that sustain regeneration. The zebrafish is well established as a system to study regeneration with the advantages of advanced genetics and in vivo imaging of living animals. Considerable progress has been made on understanding regeneration in the lateral line system, the series of mechanosensory hair cells on the surface of the body used detect water flow that share many properties with hair cells of the inner ear. By contrast there have been very few studies of hair cell regeneration in the zebrafish inner ear, mainly because there has been no reliable method for causing rapid and reproducible damage. In addition little is known about supporting cell types in the zebrafish inner ear. Overcoming both of these obstacles would establish the zebrafish inner ear as a new model for hair cell regeneration. We propose to develop tools for rapid, reproducible damage and regeneration in the zebrafish inner ear. We also propose to identify inner ear supporting cell types, including potential hair cell precursors. Successful completion of these aims will provide important tools for the community to begin new studies in zebrafish inner ear regeneration.