Zebrafish Inner Ear Regeneration

斑马鱼内耳再生

• 批准号: 10349933
• 负责人: David W Raible
• 金额: $ 22.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10349933
• 关键词: Aminoglycoside Antibiotics; Aminoglycoside resistance; Animals; Birds; Body Surface; Capsaicin; Cell physiology; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Consumption; Development; Ear; Exposure to; Fishes; Fluorescent in Situ Hybridization; Future; Gene Expression; Gene Targeting; Genetic; Genetic Models; Goals; Growth; Hair; Hair Cells; Hearing problem; Hour; Human; Inner Hair Cells; Labyrinth; Location; Mammals; Maps; Mediating; Methods; Modeling; Molecular Analysis; Natural regeneration; Nuclear; Organ; Pathway interactions; Pharmaceutical Preparations; Predisposition; Process; Property; Proteins; Reagent; Recovery; Regenerative capacity; Regenerative research; Reproducibility; Resolution; Sensory Hair; Series; Study models; Supporting Cell; System; Testing; Time; Toxic effect; Transgenic Organisms; Work; Zebrafish; cell type; equilibration disorder; experimental study; functional restoration; genetic analysis; hair cell regeneration; in vivo; in vivo imaging; lateral line; method development; postnatal development; rapid technique; regenerative; restoration; single cell analysis; single-cell RNA sequencing; tool; transcriptome sequencing; translational approach; translational therapeutics; water flow

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.

项目总结 内耳的机械感觉毛细胞丢失是导致听力和平衡障碍的主要原因。 不幸的是，毛细胞丢失是永久性的，因为人类很少或根本没有能力再生恢复头发。 细胞。尽管最近在恢复哺乳动物毛细胞方面取得了进展，这是通过促进 在发育、功能恢复过程中使用的基因和途径的表达在很大程度上是不完整的 在有限的后天发育时间内。相比之下，从鱼到鸟的非哺乳动物物种 容易地从周围的支持细胞前体中替换毛细胞。理解毛细胞的关键 再生是对维持再生的支持细胞亚群的鉴定。这个 斑马鱼作为一个研究再生的系统已经很好地建立了，它具有先进的遗传学和 活体动物的体内成像。在理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应毛细胞用来检测水流 它与内耳的毛细胞有许多共同的特性。相比之下，对头发的研究很少。 斑马鱼内耳的细胞再生，主要是因为目前还没有可靠的方法来引起 快速和可重复性的损害。此外，对斑马鱼体内支持细胞类型的了解很少 耳朵。克服这两个障碍将使斑马鱼内耳成为毛细胞的新模型 再生。我们建议开发快速、可重复的斑马鱼损伤和再生工具 内耳。我们还建议确定内耳支持细胞的类型，包括潜在的毛细胞前体。 成功完成这些目标将为社区在以下方面开始新的研究提供重要工具 斑马鱼内耳再生。