AMPHIBIAN METAMORPHOSIS: A DEVELOPMENTAL PROGRAM

两栖动物的变态：一个发育程序

• 批准号: 7209750
• 负责人: DONALD D BROWN
• 金额: $ 29.58万
• 依托单位: CARNEGIE INSTITUTION OF WASHINGTON, D.C.
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-09-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7209750
• 关键词: Accounting; Amphibia; Animal Model; Biological; Biological Metamorphosis; Biology; Biomedical Research; Brain; Caenorhabditis elegans; Cell Communication; Cell Death; Cell Proliferation; Cells; Corticotropin-Releasing Hormone; Country; DNA biosynthesis; Development; Disease; Dominant Negative Receptor; Drosophila genus; Embryonic Development; Enzymes; Event; Feedback; Gene Expression; Gene Transfer Techniques; Genes; Genetic; Genome; Growth; Health; Hormonal; Hormones; Human; Hypothalamic Hormones; Hypothalamic structure; Individual; Intestines; Investments; Iodide Peroxidase; Laboratories; Life Cycle Stages; Mediating; Methods; Modeling; Modems; Molecular; Mus; Numbers; Organ; Organism; Pancreas; Phenotype; Process; Proteins; Rana; Reporter; Response Elements; Role; Scientist; Spastic; Spinal Cord; Stem cells; Tadpoles; Techniques; Testing; Thinking; Thyroid Gland; Thyroid Hormones; Time; Transgenes; Vertebrates; Water; Xenopus laevis; Yeasts; base; cell type; gene function; mutant; programs; promoter; sperm cell; success

DESCRIPTION (provided by applicant): One of the most dramatic advances in biomedical research in the past 15 years has been the demonstration that human disorders can be studied in model organisms. This is a tribute to the investment of our country in basic biology. Genetic organisms such as yeast, Drosophila, C. elegans, and the mouse have led the way, but the organism par excellence for the study of thyroid hormone, one of the most important hormones for human health, is the amphibian, Xenopus laevis. Although vertebrates in all of the various phyla including humans require thyroid hormone (TH) to complete their life cycle, by far the most dramatic example is the role of TH in amphibian metamorphosis. TH is required absolutely for all of the remarkable changes that convert a tadpole into a frog. Many features of TH biology are identical in all vertebrates. However, the ease with which the model amphibian organism, X. laevis can be raised in the laboratory, the ability to manipulate TH levels, and the abundance of the material all make X. laevis the best model organism to study the action of TH. The mere addition of TH to the rearing water induces all of the events of metamorphosis. TH controls cell death, cell proliferation, and the remodeling of organs. Modem genetic methods are being applied to X. laevis with great success beginning with the new sperm mediated transgenesis technique of Kroll and Amaya. By expressing genes or mutant genes that interfere with metamorphosis in specific cell types the TH-controlled developmental program of a single cell type can be inhibited or activated selectively. The expression of detrimental gene products can be activated in cells at precise times in development utilizing controllable promoters. This wonderful old biological problem that previously could only be described by scientists is now yielding to modem molecular methods.

描述（由申请人提供）：过去 15 年生物医学研究中最引人注目的进展之一是证明可以在模型生物体中研究人类疾病。这是对我国基础生物学投入的致敬。酵母、果蝇、线虫和小鼠等遗传生物体处于领先地位，但最适合研究甲状腺激素（对人类健康最重要的激素之一）的生物体是两栖动物非洲爪蟾。尽管包括人类在内的所有不同门的脊椎动物都需要甲状腺激素 (TH) 来完成其生命周期，但迄今为止最引人注目的例子是 TH 在两栖动物变态中的作用。蝌蚪变成青蛙的所有显着变化都绝对需要 TH。 TH 生物学的许多特征在所有脊椎动物中都是相同的。然而，模型两栖生物 X. laevis 在实验室中饲养的容易性、操纵 TH 水平的能力以及材料的丰富性都使得 X. laevis 成为研究 TH 作用的最佳模型生物。仅仅在饲养水中添加 TH 就会诱发所有的变态事件。 TH 控制细胞死亡、细胞增殖和器官重塑。从克罗尔和阿马亚的新精子介导的转基因技术开始，现代遗传方法正在应用于非洲爪蟾，并取得了巨大成功。通过表达干扰特定细胞类型变态的基因或突变基因，可以选择性地抑制或激活单一细胞类型的TH控制的发育程序。利用可控启动子，可以在细胞发育的精确时间激活有害基因产物的表达。这个奇妙的古老生物学问题以前只能由科学家来描述，现在正在让位于现代分子方法。