MODELS OF INNER EAR MORPHOGENESIS

内耳形态发生模型

• 批准号: 6474540
• 负责人: JOHN Vincent BRIGANDE
• 金额: $ 4.2万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6474540
• 关键词: chick embryo; congenital ear disorder; developmental genetics; embryo /fetus culture; fluorescent dye /probe; histogenesis; laboratory mouse; labyrinth; nontherapeutic iontophoresis; vertebrate embryology

The vertebrate inner ear is a structurally complex organ consisting of fluid-filled ducts and toroidal canals protruding from a central vestibule. Congenital defects of inner ear morphogenesis can lead to deafness and balance disorders. This proposal aims to gain insight into the origins of congenital ear malformations by probing the molecular-genetic basis of otic vesicle morphogenesis. Our hypothesis is that gene expression domains subdivide the vertebrate otocyst into compartments that interact at boundaries to specify cell fate and pattern formation. We will fate map the chick and mouse otic cup by iontophoretic injection of fluorescent tracer dye. The fate maps will provide essential mechanistic information regarding the cellular movements responsible for conversion of the otic cup to an ovoid epithelial vesicle. This information will fill a critical void in the ear development field as it is not currently known how gene expression patterns at the placode stage correlate with those at the vesicle stage or beyond. In addition, the fate maps will provide a blueprint for the focal misexpression of a gene by retrovirus-mediated gene transfer. Our idea is that if precise boundaries of gene expression in the nascent otocyst are required for patterning the inner ear, then creation of temporally or spatially inappropriate foci of gene expression will likely perturb morphogenesis in a predictable way. A corollary goal of this proposal is to establish a mouse whole embryo culture model for studying early otic ontogeny. Experimental access to the ever-expanding list of natural and induced mutant mice would likely further our understanding of the genetic mechanisms that underlie inner ear morphogenesis and provide a basis for eliminating congenital deafness and balance disorders.

脊椎动物内耳是一个结构复杂的器官，由充满流体的管道和从中央前庭伸出的环形管组成。 内耳形态发生的先天性缺陷会导致耳聋和平衡疾病。 该建议旨在通过探测耳囊形形态发生的分子遗传基础来深入了解先天性耳朵畸形的起源。 我们的假设是，基因表达结构域将脊椎动物耳囊细胞分成隔室，以在边界相互作用以指定细胞命运和模式形成。 我们将通过荧光示踪剂染料的离子遗传学注射来命运小鸡和小鼠耳杯。 命运图将提供有关负责将耳杯转化为卵形上皮囊泡的细胞运动的基本机械信息。 该信息将填补耳朵发育场中的关键空隙，因为目前尚不知道位置阶段的基因表达模式与囊泡阶段或以后的基因表达模式如何相关。 此外，命运图将为逆转录病毒介导的基因转移提供蓝图，以使基因对基因的局灶性变形。 我们的想法是，如果需要对内耳进行模仿的新生眼囊中基因表达的精确边界，那么基因表达的时间或空间不适当的灶就可能会以可预测的方式扰动形态发生。 该建议的必然目标是建立一个小鼠整个胚胎培养模型，用于研究早期的异化。实验访问天然和诱发的突变小鼠的膨胀清单可能会进一步了解我们对内耳形态发生的遗传机制的理解，并为消除先天性耳聋和平衡疾病提供了基础。