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The Journal of Neuroscience, August 23, 2006, 26(34):8866-8874; doi:10.1523/JNEUROSCI.5191-05.2006

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Development/Plasticity/Repair
Axon Guidance by Diffusible Chemoattractants: A Gradient of Netrin Protein in the Developing Spinal Cord

Timothy E. Kennedy,^1,2 Hao Wang,¹ Wallace Marshall,¹ and Marc Tessier-Lavigne^1,3

¹Departments of Anatomy and Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143, ²Departments of Neurology and Neurosurgery and Anatomy and Cell Biology, Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4, and ³Division of Research, Genentech, South San Francisco, California 94080

Correspondence should be addressed to Marc Tessier-Lavigne, Genentech Incorporated, 1 DNA Way, South San Francisco, CA 94080. Email: marctl{at}gene.com

Gradients of diffusible long-range attractant and repellent proteins have been proposed to guide growing axons during nervous system development, but such gradients have never been visualized directly. In the embryonic spinal cord, commissural axons pioneer a circumferential trajectory to the floor plate at the ventral midline directed by secreted proteins of the netrin family. In the embryonic chick spinal cord netrin-1 mRNA is expressed by floor plate cells and netrin-2 mRNA by neural epithelial cells. Antibodies to the two netrins reveal a gradient of netrin protein directly in the path of commissural axons. The netrin-1 gradient itself extends many cell diameters dorsal to the floor plate, the site of netrin-1 expression. A similar distribution of netrin-1 protein has been detected in embryonic rat and mouse spinal cord. The detection of a gradient of netrin-1 protein supports the operation of long-range chemotropic mechanisms in the developing nervous system.

Key words: chemotaxis; tropism; tropic; growth cone; commissure; diffusion

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Received Dec. 6, 2005; revised July 19, 2006; accepted July 20, 2006.

Correspondence should be addressed to Marc Tessier-Lavigne, Genentech Incorporated, 1 DNA Way, South San Francisco, CA 94080. Email: marctl{at}gene.com

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