Extracellular signals that regulate the tangential migration of olfactory bulb neuronal precursors: inducers, inhibitors, and repellents.
Neuronal migration is an essential developmental step in the construction of the vertebrate nervous system, but the extracellular signals involved in initiating and regulating neuronal movement remain unclear. Here we report the identification of a novel astrocyte-derived migration-inducing activity (MIA). Using an in vitro assay, we show that MIA induces the migration of olfactory bulb interneuron precursors, increasing the number of migrating cells and the distance they move. We established quantitative criteria to distinguish between the biological effects of inducers, inhibitors, repellents, and attractants on migrating cells and used them to compare the effects of MIA with those of Slit, a putative repulsive guidance cue. Our analysis demonstrates that, by themselves, MIA induces and Slit inhibits migration from subventricular zone explants. However, when presented together with MIA, Slit acts as a repellent. This study shows that glial cells play a critical role in initiating and modulating the movement of neuronal precursors through the release of a diffusible protein. Moreover, this study provides evidence that the guidance of migrating neuronal precursors is an integrative process, resulting from the cooperation of distinct extracellular factors, and that the function of Slit is context dependent.
Mason
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Division of Neuroscience and Department of Neurology, Children's Hospital and Harvard Medical School, Boston Massachusetts 02115, USA.
Ito
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Corfas
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D000818:Animals; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D006023:Glycoproteins; D006133:Growth Substances / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D006133:Growth Substances; D009419:Nerve Tissue Proteins; C120566:slit protein, vertebrate