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The Journal of Neuroscience, August 1, 2000, 20(15):5792-5801
Netrin-1 Promotes Thalamic Axon Growth and Is Required for Proper Development of the Thalamocortical Projection
Janet E. Braisted1, Susan M. Catalano2, Robert Stimac1, Timothy E. Kennedy3, Marc Tessier-Lavigne3, Carla J. Shatz2, and Dennis D. M. O'Leary1 1 Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, 2 Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, and 3 Departments of Anatomy and of Biochemistry and Biophysics, University of California, San Francisco, California 94143
The thalamocortical axon (TCA) projection originates in dorsal thalamus, conveys sensory input to the neocortex, and has a critical role in cortical development. We show that the secreted axon guidance molecule netrin-1 acts in vitro as an attractant and growth promoter for dorsal thalamic axons and is required for the proper development of the TCA projection in vivo. As TCAs approach the hypothalamus, they turn laterally into the ventral telencephalon and extend toward the cortex through a population of netrin-1-expressing cells. DCC and neogenin, receptors implicated in mediating the attractant effects of netrin-1, are expressed in dorsal thalamus, whereas unc5h2 and unc5h3, netrin-1 receptors implicated in repulsion, are not. In vitro, dorsal thalamic axons show biased growth toward a source of netrin-1, which can be abolished by netrin-1-blocking antibodies. Netrin-1 also enhances overall axon outgrowth from explants of dorsal thalamus. The biased growth of dorsal thalamic axons toward the internal capsule zone of ventral telencephalic explants is attenuated, but not significantly, by netrin-1-blocking antibodies, suggesting that it releases another attractant activity for TCAs in addition to netrin-1. Analyses of netrin-1
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Key words: axon guidance; chemoattraction; DCC; dorsal thalamus; internal capsule; neocortex; neogenin; striatum; Unc5 homologs
Copyright © 2000 Society for Neuroscience 0270-6474/00/20155792-10$05.00/0
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