Control of Extracellular Matrix Assembly During Vertebrate Segmentation

Yale University, New Haven CT

Investigators

Abstract

The development and maintenance of tissues and organs involves regulated formation and remodeling of the associated connective tissue. Connective tissues are composed of secreted extracellular matrix (ECM) proteins such as Fibronectin and Collagen, and cells bind and synthesize ECM via proteins called Integrins that are positioned on the surface of the cell. Excessive connective tissue formation following heart attack reduces heart function while insufficient ECM assembly can lead to cartilage degeneration. To understand how cells regulate ECM assembly, one needs to study this process in a living organism, and the zebrafish is simple experimental proxy for the human body. This project utilizes methods to genetically alter Integrin and Fibronectin activity and to visualize and measure the movement these proteins in live zebrafish embryos using laser microscopy. Cells also adhere to each other via proteins called Cadherins, and this study includes an investigation as to how cells coordinate binding between cells and between cells and connective tissue. The outcomes of the experiments are expected to shed light on how tissues form and maintain their integrity via connective tissue synthesis. Educationally, this research project involves training for an Associate Research Scientist, a PhD student as well as undergraduate students. The Principal Investigator also mentors a biotechnology class at The Sound School, part of the New Haven Public School system. This high school has extensive aquaculture programs, and the research group at Yale is helping the biotechnology students utilize zebrafish as part the course research project.