Abstract
In the long-range neuronal migration of adult mammals, young neurons travel from the subventricular zone to the olfactory bulb, a long journey (millimeters to centimeters, depending on the species). How can these neurons migrate through the dense meshwork of neuronal and glial processes of the adult brain parenchyma? Previous studies indicate that young neurons achieve this by migrating in chains through astrocytic tunnels. Here, we report that young migrating neurons actively control the formation and maintenance of their own migration route. New neurons secrete the diffusible protein Slit1, whose receptor, Robo, is expressed on astrocytes. We show that the Slit-Robo pathway is required for morphologic and organizational changes in astrocytes that result in the formation and maintenance of the astrocytic tunnels. Through this neuron-glia interaction, the new neurons regulate the formation of the astrocytic meshwork that is needed to enable their rapid and directional migration in adult brain.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids / metabolism
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Animals
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Animals, Newborn
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Astrocytes / physiology*
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Astrocytes / ultrastructure
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Brain / cytology*
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Brain / surgery
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Brain Tissue Transplantation / methods
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Bromodeoxyuridine / metabolism
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Cell Count / methods
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Cell Movement / genetics
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Cell Movement / physiology*
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Cells, Cultured
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Coculture Techniques / methods
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Doublecortin Domain Proteins
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Gene Expression Regulation / physiology
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins / genetics
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Lateral Ventricles / cytology
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Luminescent Proteins / genetics
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Mice
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Mice, Transgenic
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Microscopy, Electron, Transmission
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Microtubule-Associated Proteins / genetics
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / physiology*
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Neurons / ultrastructure
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Neuropeptides / genetics
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Organ Culture Techniques
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Organic Chemicals / metabolism
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Roundabout Proteins
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Statistics, Nonparametric
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Transfection / methods
Substances
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Amino Acids
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Doublecortin Domain Proteins
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Glial Fibrillary Acidic Protein
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Luminescent Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Organic Chemicals
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PKH 26
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Receptors, Immunologic
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Robo2 protein, mouse
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Slit1 protein, mouse
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dolaisoleucine
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enhanced green fluorescent protein
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fluorescent protein 583
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glial fibrillary astrocytic protein, mouse
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Green Fluorescent Proteins
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Bromodeoxyuridine