DEVELOPMENT STUDIES OF THE INNER EAR

内耳的发育研究

• 批准号: 6523434
• 负责人: Donna M Fekete
• 金额: $ 25.56万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6523434
• 关键词: Retroviridae; Vesiculovirus; chick embryo; confocal scanning microscopy; congenital deafness; cyanine; developmental neurobiology; ear hair cell; epithelium; fluorescence microscopy; gene expression; gene mutation; genetic markers; histogenesis; laboratory mouse; otocyst /otolith; transfection /expression vector; vertebrate embryology

DESCRIPTION: (Adapted from the Investigator's Abstract) The goal of this research is to understand the molecular mechanisms that control patterning and cell fate determination in the developing inner ear. The inner ear, unique to vertebrates, is remarkable for the complex three-dimensional arrangement of its constituent cells, which include neurons, sensory receptors and non-sensory cells organized into tubules, ducts and other specialized tissues. It is likely that the morphogenetic mechanisms required to form such structures will be shared by vertebrates. In humans and animal models, disruption of the precise morphology of the inner ear due to congenital anomalities or disease can result in deafness, and/or difficulties with balance and equilibrium, often accompanied by profound vertigo and nausea. The PI's efforts to understand the fundamental defects that result in inner ear abnormalities are focused on both the normal processes of development and on the cascade of events that can arise as a result of a specific gene defect. The aims are to: (1) undertake a lineage analysis of the progenitor cells in the early chick otocyst to reveal when distinct cell lineages diverge, such as neurogenic vs. non-neurogenic or sensory vs. non-sensory; (2) undertake a lineage analysis of the mouse organ of Corti to determine whether hair cells and supporting cells share a common progenitor; (3) generate a fate map the chick otic cup to understand the relationships between gene expression and morphogenetic movements; and (4) force both focal and global perturbations of gene expression domains to help define the rules governing pattern formation in the eveloping inner ear. The studies will employ focal dye injections as well as infection with pseudotyped replication-defective retroviral vectors to limit gene transfer to a small number of otic cells and their progeny. The fourth aim will use replication-competent viruses to generate widespread misexpression of patterning genes. Together, the proposed studies should provide insight on the divergence of inner ear lineages and what role, if any, morphogenic movements and patterning genes play in the process. Their studies are designed to test a model of inner ear patterning that is based on the establishment of compartments and boundaries. The information provided by these animal studies may aid in understanding the molecular-genetic basis of human birth defects that cause deafness and vestibular dysfunction in humans.

描述：(改编自调查人员摘要)这一目标 研究是为了了解控制图案形成和 发育中的内耳细胞命运的决定。内耳，是 脊椎动物，以其复杂的三维排列而引人注目 组成细胞，包括神经元、感觉感受器和非感觉细胞 组织成小管、导管和其他特化组织的细胞。很有可能 形成这种结构所需的形态发生机制将是 脊椎动物共有的。在人类和动物模型中，精确的 先天畸形或疾病可导致内耳形态异常 耳聋，和/或平衡和平衡方面的困难，通常 伴随着严重的眩晕和恶心。私家侦探为了解 导致内耳异常的根本缺陷集中在两个方面 正常的发展过程和可能发生的一连串事件 是一种特定基因缺陷的结果。 其目的是：(1)进行祖细胞的谱系分析 早期雏鸡耳囊揭示不同细胞谱系分化的时间，例如 神经性与非神经性或感官与非感官；(2)进行 小鼠Corti器官的谱系分析以确定毛细胞是否 和支持细胞共享一个共同的祖细胞；(3)生成命运图 鸡耳杯了解基因表达和基因表达之间的关系 形态发生运动；以及(4)力的局域和全局扰动 基因表达结构域，以帮助定义模式形成的规则 发育中的内耳。这项研究也将采用聚焦染料注射。 AS感染伪型复制缺陷逆转录病毒载体以限制 将基因转移到少数耳聋细胞及其后代。第四个目标 将使用复制能力强的病毒来产生广泛的错误表达 形成图案的基因。 综上所述，拟议的研究应提供关于 内耳血统以及形态发生运动和图案的作用(如果有的话) 基因在这一过程中发挥了作用。他们的研究旨在测试一种内部模型 基于隔室的建立的耳图案 边界。这些动物研究提供的信息可能有助于 理解导致人类出生缺陷的分子遗传学基础 人类的耳聋和前庭功能障碍。