Molecular Basis For The Morphogenesis Of The Inner Ear

内耳形态发生的分子基础

• 批准号: 7130159
• 负责人: Doris Wu
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7130159
• 关键词: Retroviridae; biological signal transduction; bone morphogenetic proteins; chick embryo; developmental neurobiology; fibroblast growth factor; gene expression; histogenesis; labyrinth; phenotype; rhombencephalon; transcription factor; transfection /expression vector

Our major accomplishments this year are in the following areas: 1) Role of hindbrain in inner ear development Using tissue extirpation and translocation techniques in chicken embryos, we show that the hindbrain confers the dorsoventral but not anteroposterior axial information to the developing inner ear. Sonic hedgehog emanated from either the floor plate or the notochord is a major factor in dictating ventral patterning of the inner ear. Furthermore, normal dorsal otic tissues will acquire ventral fates when juxtaposed to ventral hindbrain tissues in ovo, over riding any potential dorsalizing signals from other tissues. These results suggest that hindbrain is the major tissue responsible for dictating the dorsal-ventral axis of the inner ear. 2) Role of Gbx2 in inner ear development Gbx2 is a homeobox-containing transcription factor. The absence of Gbx2 function in mice results in inner ear defects that involve both vestibular and auditory components. These inner ear phenotypes are remarkably similar to those reported in kreisler mice, which have inner ear defects attributed to defects in the hindbrain. Our gene expression analyses suggest that activation of Gbx2 expression in inner ear is an important step downstream of hindbrain signaling.

我们今年的主要成就是以下领域： 1）后脑在内耳发育中的作用 使用鸡肉胚胎中的组织灭绝和易位技术，我们表明后脑脑赋予了背腹侧腹膜，而不是前后轴向信息到发育中的内耳。从地板板或脊索散发出的声音刺猬是决定内耳腹侧图案的主要因素。此外，当与OVO中的腹侧后后脑组织并列时，正常的背膜组织将获得腹侧命运，而从其他组织中骑出任何潜在的背侧信号。这些结果表明，后脑是负责指示内耳背腹侧轴的主要组织。 2）GBX2在内耳发育中的作用 GBX2是一个含同基因的转录因子。小鼠中GBX2功能的不存在会导致内耳缺陷，涉及前庭和听觉成分。这些内耳表型与克雷斯勒小鼠中报道的那些表型非常相似，克雷斯勒小鼠的内耳缺陷归因于后脑缺陷。我们的基因表达分析表明，内耳内GBX2表达的激活是后脑信号传导下游的重要步骤。