Molecular Basis of Thyroid in Hormone Action in Brain Development

甲状腺在大脑发育中激素作用的分子基础

• 批准号: 9724080
• 负责人: Robert Denver
• 金额: $ 16.5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9724080&HistoricalAwards=false
• 关键词: Molecular; Basis; Thyroid; Hormone; Action

PI: Denver, R. IBN-9724080 Normal development of the vertebrate brain requires thyroid hormone (TH). Insufficient amounts of hormone during fetal life results in severe defects in neural development (e.g., cretinism in humans). On a global scale, congenital hypothyroidism is one of the most pervasive and detrimental human health problems, resulting in entire populations of mentally impaired ad physically stunted individuals in certain areas of the world. In addition to hypothyroidism caused by iodine deficiency, recent reports of disruptive effects on the thyroid axis of various industrially-produced compounds suggest the possibility for profound negative effects of environmental pollutants on developmental processes of humans and wildlife. The proposed research aims to understand the molecular basis of TH action on the development of the vertebrate central nervous system (CNS). Tadpoles of the African clawed frog, Xenopus laevis will be used to study TH-induced neural development and to clone TH-target genes in the CNS. This model in invaluable for understanding post-embryonic brain development since it affords easy access to all stages of development, and the basic neurodevelopmental processes are similar in frogs and other vertebrate animals including humans. The primary objectives are to: 1) understand how TH receptors transduce the hormonal signal to the cell nucleus resulting in changes in gene expression, and , 2) understand the structure and function of TH target genes in the CNS.

PI：Denver，R. IBN-9724080 脊椎动物大脑的正常发育需要甲状腺激素（TH）。 胎儿期激素量不足导致神经发育严重缺陷（例如，人类的克汀病）。 在全球范围内，先天性甲状腺功能减退症是最普遍和最有害的人类健康问题之一，在世界某些地区导致整个人口的精神受损和身体发育迟缓的个人。 除了碘缺乏引起的甲状腺功能减退症外，最近关于各种工业生产的化合物对甲状腺轴的破坏性影响的报告表明，环境污染物可能对人类和野生动物的发育过程产生深远的负面影响。 该研究旨在了解TH作用于脊椎动物中枢神经系统（CNS）发育的分子基础。 非洲爪蟾的蝌蚪将用于研究TH诱导的神经发育和克隆CNS中的TH靶基因。 这个模型对于了解胚胎后大脑发育非常有价值，因为它可以很容易地进入发育的所有阶段，并且基本的神经发育过程在青蛙和其他脊椎动物（包括人类）中是相似的。 主要目标是：1）了解TH受体如何将激素信号传递到细胞核，导致基因表达的变化，以及2）了解CNS中TH靶基因的结构和功能。