Abstract
The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific growth of granule neuron axons and parallel fiber patterning. Cdh1 RNA interference in neurons was also found to override the inhibitory influence of myelin on axonal growth. Thus, Cdh1-APC appears to play a role in regulating axonal growth and patterning in the developing brain that may also limit the growth of injured axons in the adult brain.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Axons / physiology*
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Axons / ultrastructure
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Cell Cycle
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Cell Cycle Proteins / metabolism
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Cell Nucleus / metabolism
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Cells, Cultured
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Cerebellar Cortex / cytology*
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Cerebellar Cortex / growth & development
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Dendrites / physiology
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Dendrites / ultrastructure
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Electroporation
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Morphogenesis
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Mutation
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Myelin Sheath / metabolism
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Neurons / physiology*
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Organ Culture Techniques
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RNA Interference
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Rats
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Rats, Long-Evans
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Transfection
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Ubiquitin-Protein Ligase Complexes / genetics
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Ubiquitin-Protein Ligase Complexes / metabolism*
Substances
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Cell Cycle Proteins
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Fbxo5 protein, rat
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome