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.
