A common theme of nervous system development is the selective remodeling of axonal connections. In the fruit fly, neurons that originally take on a specific larval morphology can be selectively pruned and then re-extend to form morphologically distinct adult neurons. The mechanisms regulating axon remodeling are largely unknown. Using genetics, the cellular and molecular mechanisms of axon remodeling, or more precisely, pruning and re-extension of axons will be studied. The first step will be to determine the cellular mechanism, local degeneration or retraction, mediating axon pruning by performing ultrastructural analysis through immuno-electron microscopy. Next, the molecular mechanisms of axon pruning will be studied by candidate gene and forward genetic approaches. A small-scale forward genetic screen for remodeling mutants has been performed and several lines that fail to re-extend after pruning have been identified. To study axon re-extension during remodeling, these re-extension mutants will be cloned. In addition, studying the basic mechanisms of axon pruning and re-extension may give insight into the molecular programs regulating axon degeneration during nervous system disease and axon regeneration after nerve injury.
