Zebrafish Inner Ear Regeneration

斑马鱼内耳再生

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要内耳的机械感力毛细胞损失是听力和平衡疾病的主要原因。不幸的是，毛细胞损失是永久的，因为人类几乎没有或没有再生恢复头发的能力细胞。尽管最近通过促进哺乳动物的毛细胞恢复了毛细胞的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不完整，并且在有限的产后发展窗口中。相比之下，从鱼到鸟类的非哺乳动物物种很容易从周围的支撑细胞前体中替换毛细胞。对理解毛细胞至关重要再生是支持维持再生细胞的亚群的鉴定。这斑马鱼是一个很好地确立的，可以研究再生，并具有先进遗传学的优势和在体内成像对活动物的成像。在理解再生方面取得了很大进展横向线系统，人体表面上的一系列机械感觉毛细胞检测水流与内耳的毛细胞共享许多特性。相比之下，头发的研究很少斑马鱼内耳中的细胞再生，主要是因为没有可靠的方法来引起快速且可重复的损害。此外，关于支持斑马鱼内部的细胞类型知之甚少耳朵。克服这两个障碍都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，以快速，可重复的损坏和斑马鱼的再生内耳。我们还建议识别支撑细胞类型的内耳，包括潜在的毛细胞前体。这些目标的成功完成将为社区提供重要的工具斑马鱼内耳再生。