Abstract
Axon pruning is widely used for the refinement of neural circuits in both vertebrates and invertebrates, and may also contribute to the pathogenesis of neurodegenerative diseases. However, little is known about the cellular and molecular mechanisms of axon pruning. We use the stereotyped pruning of gamma neurons of the Drosophila mushroom bodies (MB) during metamorphosis to investigate these mechanisms. Detailed time course analyses indicate that MB axon pruning is mediated by local degeneration rather than retraction and that the disruption of the microtubule cytoskeleton precedes axon pruning. In addition, multiple lines of genetic evidence demonstrate an intrinsic role of the ubiquitin-proteasome system in axon pruning; for example, loss-of-function mutations of the ubiquitin activating enzyme (E1) or proteasome subunits in MB neurons block axon pruning. Our findings suggest that some forms of axon pruning during development may share similarities with degeneration of axons in response to injury.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Axons / physiology*
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Axons / ultrastructure
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Cell Adhesion Molecules / analysis
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Cysteine Endopeptidases / physiology*
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Cytoskeletal Proteins / analysis
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Cytoskeleton / ultrastructure
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Cytosol / chemistry
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Drosophila / genetics
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Drosophila / growth & development*
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Drosophila / ultrastructure*
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Endocytosis
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Endopeptidases / genetics
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Gene Expression
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Ligases / genetics
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Ligases / physiology
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Metamorphosis, Biological / physiology*
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Microtubules / ultrastructure
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Multienzyme Complexes / physiology*
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Mutation
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Nerve Degeneration
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Neurons / metabolism
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Neurons / ultrastructure
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Proteasome Endopeptidase Complex
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Saccharomyces cerevisiae / enzymology
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Synapses / chemistry
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Transfection
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Ubiquitin / physiology*
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Ubiquitin-Activating Enzymes
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Ubiquitin-Protein Ligases
Substances
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Cell Adhesion Molecules
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Cytoskeletal Proteins
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Multienzyme Complexes
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Ubiquitin
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Ubiquitin-Protein Ligases
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Endopeptidases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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ubiquitin-Nalpha-protein hydrolase
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Ligases
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Ubiquitin-Activating Enzymes