February 11, 2003
Tuesday - 3:00 pm in Swain West 238
Speaker: Dr. Shane Hutson, Duke Free Electron Laser Lab
Title: Measuring the forces that drive morphogenesis through quantitative laser-microsurgery
Abstract:
Forces generated within developing embryos drive the cell shape changes and movements required for morphogenesis, the development of organismal form. We are investigating the forces at play in the morphogenetic process of dorsal closure in transgenic embryos of the fruit-fly, Drosophila melanogaster. Dorsal closure serves as a model system with clear parallels to both vertebrate development and wound healing. To investigate these forces, we have developed a quantitative laser-microsurgery system. A near diffraction-limited, computer-steered UV-microbeam is used to ablate tissues in the embryo with sub-cellular resolution. The response of an embryo to this mechanical perturbation is tracked in real-time via laser-scanning confocal microscopy. By designing laser-incisions that remove one or more forces in an embryo, we upset the quasi-equilibrium that existed before the cut. The tissues of the embryo respond by adopting a new geometry characteristic of the new force balance. By measuring the resulting changes in tissue geometry, we can infer the magnitude and direction of the forces we removed. Thus, when combined with advanced image-processing techniques and quantitative modeling, laser-microsurgery becomes a powerful tool for probing the physical forces underlying morphogenesis. When applied to dorsal closure, we show that this process is driven by multiple cellular forces that are coordinated in both space and time. Furthermore, we have developed a quantitative rate-process model that empirically captures the synergy and synchronization between these forces. This model provides a physical framework for understanding the phenotypes of Drosophila mutants in which dorsal closure fails, a key step towards connecting morphogenesis to the genetic program of development.