ATONAL AND MATH1 AND CNS AND PNS DEVELOPMENT

无调性和数学 1 以及 CNS 和 PNS 发展

• 批准号: 6151526
• 负责人: BASSEM A HASSAN
• 金额: $ 3.92万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6151526
• 关键词: Drosophilidae; biochemical evolution; central nervous system; developmental genetics; developmental neurobiology; gene expression; gene targeting; genetically modified animals; histology; laboratory mouse; labyrinth; linkage mapping; peripheral nervous system

Conserved mechanisms appear to be responsible for the control of neural development in vertebrates and invertebrates. The atonal (ato) gene is an important regulatory switch for chordotonal organ formation in the peripheral nervous system (body wall, joints, auditory structures) of Drosophila. Several vertebrate homologues of ato have been described. The mouse Math1 gene shares the highest homology with ato when compared to the other mouse homologues. Expression studies have shown a striking conservation of the expression pattern between ato and Math1 in the two species: both genes are expressed in mechanotransducing organs of the body wall, joints, and auditory system. However, Math1 has also been shown t be expressed and required for the external granular layer of the cerebellum. No expression has been demonstrated for ato in the mid brain of Drosophila. I have shown that ato is indeed expressed in the fly CNS, and identified a CNS specific enhanced for ato. In addition, in collaboration with Dr. Huda Zoghbi's and Dr. Ruth Anne Eatock's labs, we have demonstrated a function for Math1 in the vertebrate ear. Thus the conservation between the two genes is not only structural, but also functional in developmental terms. i am proposing experiments to analyze the function of ato and Math1 in the tissues where their functions are not understood: the fly brain and the mouse inner ear. These studies will utilize the powerful genetics of Drosophila and the wealth of embryological analysis in the mouse inner ear, as well as techniques for histology and molecular biology to address the questions proposed, Understanding the mechanisms of neural development is important for understanding the pathologies that may result from perturbing normal development, as well as for designing effective treatment.

保守机制似乎负责神经的控制。 脊椎动物和无脊椎动物的发育。无调性(ATO)基因是一种 中枢神经系统中节律器官形成的重要调节开关 外周神经系统(体壁、关节、听觉结构) 果蝇。已经描述了几个ATO的脊椎动物同源物。这个 小鼠Math1基因与ATO的同源性最高 其他老鼠的同源物。表情研究表明，一个惊人的 ATO和Math1在两者中表达模式的保守性 物种：这两个基因都在身体的机械转换器官中表达 墙壁、关节和听觉系统。然而，Math1也被证明是 在小脑的外部颗粒层表达和必需。 未见ATO在大鼠中脑中的表达 果蝇。我已经证明ATO确实在苍蝇中枢神经系统中表达，并且 已确定针对ATO的中枢神经系统特异性增强。此外，在协作中 Huda Zoghbi博士和Ruth Anne Eatock博士的实验室，我们有 证明了Math1在脊椎动物耳朵中的功能。因此， 这两个基因之间的保守不仅是结构性的，而且 从发展的角度来看，具有功能性。我提出了一些实验来分析 ATO和Math1在非功能组织中的功能 了解：苍蝇脑和小鼠内耳。这些研究将 利用果蝇强大的遗传学和丰富的 小鼠内耳的胚胎学分析，以及 组织学和分子生物学来解决提出的问题， 了解神经发育的机制对于 了解扰乱正常可能导致的病理 发展，以及设计有效的治疗方法。