Life and death decisions in Drosophila neural stem cells

Massachusetts General Hospital, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): The life or death decision of individual cells is critical for the proper development of the whole organism. While the elimination of superfluous cells is essential to prevent hypertrophy in the developing central nervous system, it is equally important that necessary cells survive. How some cells survive among a pool of similar cells that die is a poorly understood aspect of development. Drosophila provides an outstanding model to investigate how specific cells in the developing central nervous system are selected to survive while others die, due to the extensive foundation of information about neural development, the availability of genetic approaches to manipulate apoptosis in the developing animal, and the ease of open- ended screens. We have shown that specific neural stem cells are eliminated by apoptosis during embryogenesis in the fly. We have characterized the regulatory and effector pathways important for this death. Here, we propose to look at this developmental death from the other side: what preserves the subset of stem cells that survive? Genetic, histological and molecular approaches will be used to define the pathways responsible for the survival of individual stem cells in the context of the developing nervous system. These studies will determine the mechanisms that some cells use to avoid cell death in development and may provide insight into the treatment of human diseases such as neurodegeneration and cancer.