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

$347,019FY2008BIONSF

California State L A University Auxiliary Services Inc., Los Angeles CA

Investigators

Abstract

Robert M. Nissen Proposal #IOS-0744454 RUI: Exploring the role of the Wdr68-Dyrk1b complex in Nodal signaling One 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.

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