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The Journal of Neuroscience, October 1, 2001, 21(19):7654-7663
Extracellular Signals That Regulate the Tangential Migration of
Olfactory Bulb Neuronal Precursors: Inducers, Inhibitors, and
Repellents
Heather A.
Mason1,
Susumu
Ito2, and
Gabriel
Corfas1
1 Division of Neuroscience and Department of Neurology,
Children's Hospital and Harvard Medical School, Boston Massachusetts
02115, and 2 Department of Neurobiology, Harvard Medical
School, Boston, Massachusetts 02115
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.
Key words:
neuronal migration; chain migration; olfactory bulb; subventricular zone; Slit; astrocytes
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197654-10$05.00/0
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