Cellular and molecular mechanisms of dendrite pruning in Drosophila

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The nervous system needs to be accurately wired together to function properly. During development nerve cells (neurons) often overgrow forming many branches, each of which makes connections with many different cells. Some of these branches are redundant or inappropriate and need to be removed for neural circuits to work well. This removal of branches is termed pruning. We have shown that during metamorphosis fruit flies prune back the branches of their sensory neurons by a local degeneration. This pruning looks very similar to degeneration found in nerves following injury or that seen in diseases like Alzheimer?s. Circulating blood cells remove branches by engulfing (eating) them. Our preliminary data shows that the molecular machinery normally used by a cell to commit ?cellular suicide? (apoptosis) is activated locally in the branches that need to be removed. During apoptosis a cell disassembles itself in an orderly manner and signals to other cells in the body to eat it whole. In pruning neurons this machinery appears to be tightly regulated to prevent the cell dying. Blocking the machinery suppresses the removal of the branches, suggesting that it is important for flagging branches to be eaten by blood cells. The work described here will establish how the ?apoptotic machinery? is switched on in these branches and how this tells the blood cells to eat only those regions of the cell. We hope this will also tell us something about way which neurons degenerate during disease, which could ultimately help cure people. We will make our results available to the public by publishing significant advances on our website, through press releases and by giving talks.