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The Journal of Neuroscience, May 1, 2002, 22(9):3568-3579

Deleted in Colorectal Carcinoma and Differentially Expressed Integrins Mediate the Directional Migration of Neural Precursors in the Rostral Migratory Stream

Shin-ichi Murase and Alan F. Horwitz

Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908

Precursors of the olfactory interneurons migrate from the subventricular zone via the rostral migratory stream (RMS). To investigate the molecular mechanisms by which RMS cells migrate, we used a slice preparation, which allows the migrating cells to be imaged at very high temporal and spatial resolution in the presence of added inhibitors. Using immunohistochemistry, we first determined that the 1-, 8-, and 1-integrin subunits and the 5- and 1-laminin subunits are expressed during embryonic day 16 to the early postnatal stage. During early postnatal days, v- and 6-integrins appeared, and their expression persisted throughout adulthood. The migrating cells also expressed the netrin receptors neogenin and Deleted in Colorectal Carcinoma (DCC). Netrin-1 is expressed in olfactory mitral cells. Anti-integrin antibodies inhibited the production of protrusions as well as cellular translocation. In contrast, anti-DCC antibodies primarily altered the direction of the protrusions; consequently, the migration was no longer unidirectional, and the speed was reduced. Thus, the interaction of DCC, possibly through an interaction with netrin-1, contributes to the direction of migration by regulating the formation of directed protrusions. In contrast, the integrins function in production of protrusions and cellular translocation, with different integrins participating at different developmental stages.

Key words: chemoattraction; neural cell adhesion molecule; slice culture; video microscopy; radial glia; time-lapse recording; polysialic acid

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2293568-12$05.00/0

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