Negative Regulation of TGFß Signaling by a Fast1-Groucho Corepressor Complex

胚胎发育的一个重要步骤是形成初级胚层，即内胚层、中胚层和外胚层，这些胚层产生了许多不同类型的细胞，构成人体的器官和组织。这一建议侧重于调节中胚层形成的遗传途径，中胚层形成心脏、肌肉、血液、骨骼和肾脏。Fast1是一种调节其他基因表达的基因，控制着胚胎中胚层的发育。该项目的目标是通过确定Fast1何时何地起作用，通过识别由Fast1调节的其他基因，以及通过定义与Fast1一起控制中胚层形成的蛋白质，来确定Fast1在中胚层形成中的作用。以两栖动物胚胎为模型，采用生化和分子方法检测Fast1的功能，并通过对青蛙胚胎的处理来确定Fast1的发育功能。这些研究将揭示Fast1在胚胎中胚层形成中的新功能。这些研究的意义在于确定胚胎发育的基本机制。除了深入了解胚胎发育之外，这个项目还将产生更广泛的影响，为本科生科学家以及本科生和研究生水平上代表性不足的少数民族提供研究培训机会。学生将直接受益于在板凳上的动手训练，并接触到科学的方法。这样，拟议的研究将实现教学和培训年轻科学家的目标，以及扩大代表性不足的群体参与基础研究的目标。

An important step in embryonic development is the formation of the primary germ layers, endoderm, mesoderm and ectoderm, which give rise to the many different cell types of the organs and tissues of the body. This proposal focuses on the genetic pathways that regulate mesoderm formation, which forms the heart, muscles, blood, bones and kidneys. Fast1, a gene that regulates the expression of other genes, controls mesodermal development in the embryo. The goal of this project is to define the role of Fast1 in mesoderm formation by determining when and where Fast1 functions, by identifying other genes regulated by Fast1, and by defining proteins that together with Fast1 control mesoderm formation. Using amphibian embryos as a model, biochemical and molecular approaches will be used to examine Fast1 function, and manipulation of the frog embryo will be used to determine the developmental function of Fast1. The proposed studies will reveal new functions of Fast1 in the formation of embryonic mesoderm. The significance of these studies is in defining the basic mechanisms of embryonic development. In addition to yielding insight into embryonic development, this project will have a broader impact by providing research-training opportunities for undergraduate scientists, and for under-represented minorities at the undergraduate and graduate levels. Students will receive the direct benefit of hands on training at the bench, and exposure to the scientific method. In this way, the proposed research will accomplish the goals of teaching and training young scientists, and of broadening the participation of under-represented groups in basic research.