DEVELOPMENT STUDIES OF THE INNER EAR

描述：（改编自研究者摘要） 研究是为了了解控制模式的分子机制， 内耳发育中的细胞命运决定。内耳是 脊椎动物，是显着的复杂的三维排列，其 组成细胞，包括神经元，感觉受体和非感觉 细胞组织成小管、导管和其他特化组织。很可能 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， 由于先天性异常或疾病导致的内耳形态 耳聋和/或平衡困难， 伴有严重的眩晕和恶心PI努力了解 导致内耳异常的基本缺陷集中在两个方面 正常的发展过程和可能出现的一连串事件， 是由于某种特定的基因缺陷 目的是：（1）进行祖细胞谱系分析， 早期鸡耳囊肿，以揭示不同的细胞谱系何时分化，如 神经源性与非神经源性或感觉与非感觉;（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）生成一个命运图， 鸡耳杯，以了解基因表达之间的关系， 形态发生运动;和（4）迫使焦点和全球扰动 基因表达结构域，以帮助定义规则的模式形成， 发育中的内耳这些研究也将采用局部染料注射 作为假型复制缺陷型逆转录病毒载体的感染， 基因转移到少量的耳细胞及其后代。第四个目标 将使用复制能力的病毒来产生广泛的错误表达， 模式基因 总之，拟议的研究应该提供关于以下分歧的见解： 内耳谱系和什么样的作用，如果有的话，形态发生运动和模式 基因在这个过程中发挥作用。他们的研究旨在测试一种内在的 耳朵模式是建立在隔间的基础上， 边界这些动物研究提供的信息可能有助于 了解人类出生缺陷的分子遗传基础， 耳聋和前庭功能障碍。

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.