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Directional guidance of neuronal migration in the olfactory system by the protein Slit

Nature volume 400, pages 331–336 (1999)Cite this article

Abstract

Although cell migration is crucial for neural development, molecular mechanisms guiding neuronal migration have remained unclear. Here we report that the secreted protein Slit repels neuronal precursors migrating from the anterior subventricular zone in the telencephalon to the olfactory bulb. Our results provide a direct demonstration of a molecular cue whose concentration gradient guides the direction of migrating neurons. They also support a common guidance mechanism for axon projection and neuronal migration and suggest that Slit may provide a molecular tool with potential therapeutic applications in controlling and directing cell migration.

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Figure 1: Repulsion of SVZa neurons by the septum and the floorplate and expression of slit genes in the postnatal septum.
Figure 2: Effect of Slit on neurons migrating from SVZa explants.
Figure 3: Neuronal nature and distribution of SVZa neurons.
Figure 4: Spatial relationship between SVZa explants and Slit-expressing cells.
Figure 5: Migration of neurons in the RMS.
Figure 6: Inhibition of the repulsive activity in the septum by RoboN.

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Acknowledgements

We thank W. Yuan and D. Ornitz for mouse slit cDNAs; J. Xu, Q. Wang and L. Zhou for help with in situ hybridization; W. Gan and J. Lichtman for help with confocal imaging and analysis; J.Brunstrom and A. Pearlman for discussions; C. S. Goodman and M. Tessier-Lavigne for comments; NIH, NSFC and SCST for support; and the John Merck Fund, NSFC and the Leukemia Society of America for scholar awards (to Y.R. and J.Y.W.).

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Authors and Affiliations

  1. Laboratory of Molecular Neurobiology, Shanghai Research Center for the Life Sciences and The National Institute of Neuroscience, The Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai, China

    Wei Wu & Jin-hui Chen

  2. Department of Anatomy and Neurobiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8108, 660 S. Euclid Avenue, St Louis, 63110, Missouri, USA

    Kit Wong & Yi Rao

  3. Departments of Pediatrics, and Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8108, 660 S. Euclid Avenue, St Louis, 63110, Missouri, USA

    Zhi-hong Jiang, Sophie Dupuis & Jane Y. Wu

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Correspondence to Jane Y. Wu or Yi Rao.

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Wu, W., Wong, K., Chen, Jh. et al. Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 400, 331–336 (1999). https://doi.org/10.1038/22477

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