RUI: IOS/Exploring the Role of the Wdr68-Dyrk1b Complex in Nodal Signaling

Robert M. Nissen Proposal #IOS-0744454 RUI：探索Wdr 68-Dyrk 1b复合物在Nodal信号传导中的作用发育中的胚胎必须做出的最早决定之一是将其细胞的哪一部分提交给三种不同的“生殖”谱系中的每一种，即外胚层，中胚层和内胚层。Nissen实验室试图更好地了解这些极早期细胞命运决定的基本机制。虽然外胚层细胞产生皮肤和脑，但中胚层和内胚层细胞产生大多数其他组织，包括心脏，肝脏和肌肉。“Nodal信号传导途径”在决定致力于中胚层和内胚层的细胞数量方面起关键作用，并且以外胚层细胞为代价。因此，精确控制Nodal信号通路活性的量对于维持许多成体组织之间的适当平衡是重要的。Nodal信号通路由一系列基因组成，其顺序功能是接收、处理、传输和执行关于有多少细胞向中胚层和内胚层命运提交的命令。尽管对Nodal信号通路的理解很大，但参与处理和传递命令信号的几个基因还没有很好地理解，一些基因可能仍然没有被识别。该项目的重点是探索两个最近发现的基因wdr 68和dyrk 1b在Nodal信号通路中的作用。 拟议的研究在斑马鱼模式生物中结合了遗传和生化方法。由于受精是外部的，而且鱼产卵，因此很容易在斑马鱼中观察到胚胎发育的早期阶段。对整合研究和教育的更广泛的影响是，这些研究正在联邦指定的标题III和西班牙裔服务机构进行。这些主要是女性和少数民族学生直接参与研究项目，从而加强了他们的科学教育和我们对胚胎发育的了解。 此外，由于这项工作的性质，这项研究对再生医学疗法的发展有影响。

Robert M. NissenProposal #IOS-0744454RUI: Exploring the role of the Wdr68-Dyrk1b complex in Nodal signalingOne of the earliest decisions a developing embryo must make is what fraction of its cells to commit to each of three distinct "germ" lineages known as the ectoderm, mesoderm and endoderm. The Nissen lab seeks to better understand the fundamental mechanisms governing these extremely early cell fate decisions. While ectoderm cells give rise to skin and brain, mesoderm and endoderm cells give rise to most other tissues including heart, liver and muscle. The "Nodal signaling pathway" plays a critical role in determining the number of cells devoted to mesoderm and endoderm and does so at the expense of ectoderm cells. Hence, precise control over the amount of Nodal signaling pathway activity is important to maintaining the proper balance between many adult tissues. The Nodal signaling pathway is composed of a series of genes whose sequential functions are to receive, process, transmit and execute the command regarding how many cells to commit towards mesoderm and endoderm fates. Although a significant amount is understood about the Nodal signaling pathway, several genes involved in processing and transmitting the command signal are not well understood and some genes likely remain unidentified. The focus of this project is to explore the roles that two recently identified genes, wdr68 and dyrk1b, play in the Nodal signaling pathway. The proposed research uses a combination of genetic and biochemical approaches in the zebrafish model organism. Since fertilization is external and because fish lay their eggs, the very early stages of embryonic development are easily observed in zebrafish. The Broader Impacts on integrating research and education are that these studies are being performed at a federally designated Title III and Hispanic Serving Institution. These predominantly female and minority students are directly engaged in the research project, thereby enhancing their science education and our knowledge about embryonic development. In addition, because of the nature of the work, the research has implications for the development of regenerative medical therapies.