Spatially Regulated Translation of the Maternal xCR1 mRNA During Xenopus Development

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

Intellectual Merit: The embryos of organisms with backbones (vertebrates) begin life essentially as balls of cells. To form specific adult tissues and structures, the cells of the embryos must receive specific instructions that direct the synthesis of particular molecules at particular times and places. In many cases, these important instructions are themselves molecules. They are called messenger RNAs (mRNAs) and they transmit the information encoded in DNA from a cell's nucleus to its cytoplasm for synthesis of proteins, the cell's workhorse molecules. The goal of this project is to elucidate the fundamental mechanisms for regulating this process. The studies will be carried out in the embryos of the frog, Xenopus, a convenient model organism, focusing on an mRNA molecule which directs the synthesis of an important protein called Cripto-1. The Cripto-1 protein and the steps leading to its synthesis are equally important for embryos of all vertebrates. In previous work, the research team discovered that the synthesis of the Cripto-1 protein from its mRNA is highly regulated and occurs only in a specific set of embryonic cells. The project is designed to elucidate the mechanisms of this regulation in molecular terms. Critical preliminary results showed that this regulation involves binding of a protein called Bicaudal-C (Bic-C) to specific regions of the Cripto-1 mRNA, ensuring that the Cripto-1 protein is synthesized only at the correct time and in the appropriate cells. The project will define the molecular determinants for specific recognition of Cripto-1 mRNA by Bic-C and how this binding stimulates synthesis of Cripto-1 protein. Broader Impact: This project addresses a fundamental research question of wide interest that will enhance student participation and training in scientific research at all levels (undergraduate, graduate, and post-doctoral). The PI will personally supervise students and ensure that they engage in intellectually meaningful and technically rigorous ways with all aspects of the research. The overriding educational goal is to foster the intellectual growth of students at all stages and ensure steady progress toward scientific independence. For participating undergraduate students, the goal is completing a Senior Honors Thesis by graduation. For graduate students, the goal is strong publications and preparation for careers in research. The collaborative nature of the work and the strong scientific community at UW Madison, representing a wide range of approaches and styles of research, will further enhance student education. The PI will actively recruit students that are members of under-represented minorities through University of Wisconsin programs. Furthermore, the PI has a strong record of training female Ph.D students and postdoctoral scientists and will continue to encourage the participation of women in the research. The PI will continue to be actively involved in public science education by giving seminars and providing information to several non-academic groups including local chapters of the March of Dimes. In addition, the PI will perform outreach activities to local elementary schools that promote inquiry-based approaches to science learning. The PI will lead activities involving observation and analysis of the development of live frog embryos. The effectiveness of outreach activities will be evaluated by measuring the changes in attitude toward science and learning about science among participating teachers and students.