Abstract
Slit proteins have previously been shown to regulate axon guidance, branching, and neural migration. Here we report that, in addition to acting as a chemorepellant for cortical axons, Slit1 regulates dendritic development. Slit1 is expressed in the developing cortex, and exposure to Slit1 leads to increased dendritic growth and branching. Conversely, inhibition of Slit-Robo interactions by Robo-Fc fusion proteins or by a dominant-negative Robo attenuates dendritic branching. Stimulation of neurons transfected with a Met-Robo chimeric receptor with Hepatocyte growth factor leads to a robust induction of dendritic growth and branching, suggesting that Robo-mediated signaling is sufficient to induce dendritic remodeling. These experiments indicate that Slit-Robo interactions may exert a significant influence over the specification of cortical neuron morphology by regulating both axon guidance and dendritic patterning.
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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Animals
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Cell Communication / physiology*
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Cell Differentiation / physiology*
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / embryology*
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Cerebral Cortex / metabolism
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Chemotaxis / genetics*
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Fetus
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Gene Expression Regulation, Developmental / physiology
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Structure, Tertiary / physiology
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Rats
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Rats, Long-Evans
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Roundabout Proteins
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Signal Transduction / genetics
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Transfection
Substances
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Peptide Fragments
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Receptors, Immunologic
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Robo2 protein, mouse
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Slit1 protein, mouse
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Slit1 protein, rat
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Slit3 protein, mouse
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Slit3 protein, rat
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Slit homolog 2 protein