Heart Tube Formation in Drosophila

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

Investigators

Abstract

Sunita Gupta Kramer, PhD Proposal No: 0744165 Title: Heart Tube Formation in Drosophila Formation of vascular structures involves a series of complex changes in cellular architecture. Blood vessels are essentially small tubes formed by a monolayer of endothelial cells enclosing a central lumen. How do groups of unorganized endothelial cells migrate to their proper location 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 that occur in the developing organism remain relatively unknown. The heart tube of the fruit fly, Drosophila melanogaster, provides a simple and elegant genetic model to discover the molecules and mechanisms of 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 meet at the midline to form a tube with a central lumen. Dr. Kramer has established that the guidance molecule Slit is a good candidate for playing an important role in heart tube lumen formation. Slit is a secreted extracellular molecule that is common to both insects and humans and has been shown to guide migrating cells in many different tissues in the developing organism. Dr. Kramer has found that Slit and its receptor protein Roundabout are expressed in the developing Drosophila heart at the time of lumen formation, and that defects in lumen formation occur in embryos missing these genes. These results indicate that Slit and Roundabout play an important role in this process. However, the precise mechanism by which they affect heart tube formation 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 genes that are functioning in the Slit and Roundabout pathway. It is highly likely that these mechanisms are conserved and will shed light on lumen formation in vertebrate vascular structures. In terms of Broader Impacts, the fruit fly provides a powerful and tractable genetic 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 training students from diverse backgrounds.