Investigating Cell Adhesion During Heart Tube Formation in Drosophila

Rutgers, The State University Of New Jersey-Rbhs-Robert Wood, Piscataway NJ

Investigators

Abstract

Formation of vascular structures such as blood vessels involves a series of complex cell shape changes. Blood vessels are essentially small tubes formed by a monolayer of endothelial cells enclosing a central space or lumen. How do groups of unorganized endothelial cells migrate to their proper location in the developing embryo and then arrange themselves into a linear tube with a central lumen? While experiments in cultured cells have led to a speculative model for lumen formation, surprisingly the cellular and molecular mechanisms responsible for lumen formation in the developing organism remain relatively unknown. The heart of the fruit fly, Drosophila melanogaster, provides a simple and elegant genetic model to discover the molecules and mechanisms of vascular assembly and lumen formation. During Drosophila heart tube development, the alignment of cardiac cells at the dorsal midline of the embryo is the first of two important steps in heart tube assembly. Following alignment, these cells migrate to the dorsal midline to form a linear tube with a central lumen. Dr. Kramer has established that the guidance molecule Slit and its receptors Robo and Robo2 are required during both steps of heart tube assembly. During the first step, Slit, Robo and Robo2 are required to maintain adhesion between cardiac cells during their dorsal migration. During the second step, Dr. Kramer has found that Slit and Robo are also required to negatively regulate E-Cadherin-mediated cell adhesion between neighboring cardiac cells, allowing for the formation of a lumen. However, the precise mechanism by which Slit and Robo are regulating cell adhesion in the heart has yet to be determined. To address this problem, Dr. Kramer will carefully analyze heart tube formation in embryos that are mutant for these genes as well as use the power of Drosophila genetics to identify other proteins that are functioning with Slit and Robo receptors during cell adhesion. It is highly likely that these mechanisms are conserved and that the outcomes of this work will shed light on lumen formation in vertebrate vascular structures. The broader impacts of this work rest on the fact that the fruit fly is a powerful and tractable model system not only for the study of vascular development, but also as a teaching tool for training PhD students and for introducing undergraduate students to basic science. Dr. Kramer has a strong record of involving undergraduate and graduate students in her research and is committed to teaching and training students from diverse backgrounds.