Regulation of Cortical Dendrite Development by Slit-Robo Interactions

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 i...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2002-01, Vol.33 (1), p.47-61
Main Authors: Whitford, Kristin L., Marillat, Valérie, Stein, Elke, Goodman, Corey S., Tessier-Lavigne, Marc, Chédotal, Alain, Ghosh, Anirvan
Format: Article
Language:English
Subjects:
Animals
Brain
Cell Communication - physiology
Cell Differentiation - physiology
Cells, Cultured
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Cerebral Cortex - metabolism
Chemotaxis - genetics
Dendrites - metabolism
Dendrites - ultrastructure
Fetus
Gene Expression Regulation, Developmental - physiology
Insects
Intercellular Signaling Peptides and Proteins
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurons
Peptide Fragments - genetics
Peptide Fragments - metabolism
Protein Structure, Tertiary - physiology
Rats
Rats, Long-Evans
Receptors, Immunologic - genetics
Receptors, Immunologic - metabolism
Robo protein
Rodents
Roundabout Proteins
Signal Transduction - genetics
Slit1 protein
Software
Transfection
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(01)00566-9