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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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