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The Journal of Neuroscience, August 1, 1999, 19(15):6417-6426

Local Presentation of Substrate Molecules Directs Axon Specification by Cultured Hippocampal Neurons

Teresa Esch1, Vance Lemmon2, and Gary Banker3

1 Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia 22908, 2 Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975, and 3 Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, Oregon 97201-3098

Axon specification is a crucial, early step in neuronal development, but little is known about how this event is controlled in vivo. To test the hypothesis that local presentation of growth-promoting molecules can direct axon specification, we cultured hippocampal neurons on substrates patterned with stripes of poly-L-lysine and either laminin (LN) or the neuron-glia cell adhesion molecule (NgCAM). Although undifferentiated neurites contacted both substrates equally, axons formed preferentially on LN or NgCAM. Time-lapse studies revealed that changes in the growth pattern of a cell indicative of axon specification began almost immediately after the growth cone of one of the neurites of the cell contacted LN or NgCAM. When cells were plated on alternating stripes of LN and NgCAM, cells with their somata on LN usually formed axons on NgCAM, whereas those with somata on NgCAM preferentially formed axons on LN. This suggests that the change from one axon-promoting substrate to another also provides a signal sufficient to specify the axon. These results demonstrate that contact with preferred substrate molecules can govern which neurite becomes the axon and thus direct the development of neuronal polarity.

Key words: neuronal development; polarity; NgCAM; laminin; axonal specification; hippocampal cultures


Copyright © 1999 Society for Neuroscience  0270-6474/99/19156417-10$05.00/0


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