The work proposed here aims to explore the explore the role of the cytoskeleton in retinal development using Drosophila as a model system. Considerable evidence from many labs, including ours, implicates the cytoskeleton, especially actin and actin binding proteins, in critical events, of retinal development, including morphogenesis of the photosensitive membrane and the control of cell-cell and cell-substrate contacts during development. We propose to use the special genetic and molecular methods available in Drosophila to closely describe, and where possible, to make in vivo, functional tests of the role of the cytoskeleton in retinal development. Our long term goal is an integrated understanding of cytoskeletal mechanisms of retinal development. We have developed three lines of work that converge on the cytoskeleton of the developing Drosophila eye. We have made a survey of the changing organization of the cytoskeleton during eye development. Major changes occur at critical times, including the generation of photoreceptors and the differentiation of their photoreceptive membranes, the rhabdomere. Second, we have made transgenic flies which express the actin-severing protein, gelsolin, under the control of a heat-shock promoter and have observed disruptions of rhabdomere and the dissolution of retinal stress fibers upon heat shock. Third, we have observed profound disturbances in the rhabdomere of flies with reduced levels of alpha-actinin, a central member of the actin binding protein family. In addition to their intrinsic interest, the studies proposed here connect with several major areas of cell biology; the integration of these topics into Drosophila retinal development, and future, more detailed work will require the baseline descriptions sought here. Despite their obvious and clinically significant differences, a growing number of parallels are being found to operate in the cell and molecular biology of both Drosophila and vertebrate eye development. The cytoskeleton lies at the intersection of numerous fundamental processes, and appropriate to its central role, is highly conserved; the cell biology of the cytoskeleton and the and molecules that effect it are strikingly similar in both vertebrates and invertebrates. The work proposed here will help build a foundation for genetic, molecular and cellular studies of the cytoskeleton in retinal development and pathology.
Showing the most recent 10 out of 13 publications
