MATH 1 AND CNS AND PNS DEVELOPMENT

数学 1 以及 CNS 和 PNS 发展

• 批准号: 6012782
• 负责人: Vincent Yat-Chung Wang
• 金额: $ 2.31万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6012782
• 关键词: alleles; brain stem; cell differentiation; central nervous system; developmental neurobiology; gene expression; gene targeting; genetic mapping; genetic markers; immunocytochemistry; inbreeding; laboratory mouse; neurogenesis; neurogenetics; neuropathology; peripheral nervous system; phenotype; protein structure function; respiration regulatory center; respiratory function; respiratory insufficiency /failure; rhombencephalon

In Drosophila, atonal encodes a basic helix-loop-helix (bHLH) protein essential for the development of chordotonal organs (sensory organs for proprioception, balance and audition). The mouse atonal homolog 1 (Math1) is expressed in the hindbrain, dorsal neural tube, inner ear, Merkel cells, and joints. Gene targeting in mice revealed that Mah1 is essential for the genesis of cerebellar granule neurons and inner ear hair cells. Furthermore, Math1 null nice die shortly after birth because of inability to breathe. To investigate the influence of Math1 on the differentiation of neurons involved in respiratory control, we will assess the neurophysiological integrity of the respiratory circuitry in Math1 null embryos, fate-map embryonic brainstem neurons that express Math1 null newborns die quickly, we will also target atonal into the Math1 locus to ascertain which facets of the phenotype can be rescued. Complete rescue will identify the bHLH domain as the mediator of Math1 function; partial rescue will indicate that other portions of the protein are necessary in the mammal. These data will allow future analysis of molecular interactions in the development of the brainstem, cerebellum and inner ear hair cells, with ramifications for understanding cerebellar anomalies, deafness, balance disorders, and neonatal breathing dysfunctions.

在果蝇中，无性激素编码一种基本的螺旋-环-螺旋(BHLH)蛋白，对于脊索器官(本体感觉、平衡和听力的感觉器官)的发育是必不可少的。小鼠无张力同系物1(Math1)在后脑、背侧神经管、内耳、Merkel细胞和关节中表达。小鼠的基因打靶显示，Mah1对小脑颗粒神经元和内耳毛细胞的发生是必不可少的。此外，Math1在出生后不久就因为无法呼吸而死亡。为了研究Math1对参与呼吸控制的神经元分化的影响，我们将评估Math1缺失胚胎呼吸回路的神经生理学完整性，表达Math1缺失新生儿的命运图胚胎脑干神经元迅速死亡，我们还将靶向Math1基因座以确定哪些方面的表型可以被拯救。完全修复将确定bHLH域是Math1功能的中介；部分修复将表明该蛋白的其他部分在哺乳动物中是必需的。这些数据将使未来能够分析脑干、小脑和内耳毛细胞发育过程中的分子相互作用，从而有助于理解小脑异常、耳聋、平衡障碍和新生儿呼吸功能障碍。