Abstract
Guidance cues and signal transduction mechanisms acting at the nerve growth cone are fairly well understood, but the intracellular mechanisms operating to change the direction of axon outgrowth remain unknown. We now show that growth cones integrate myosin II–dependent contraction for rapid, coordinated turning at borders of laminin stripes in response to signals from laminin-activated integrin receptors; in the absence of myosin II activity, outgrowth continues across the borders.
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Acknowledgements
G. Philips and D. Morris provided technical support. We thank J. Cooper for comments on the manuscript. The US National Institutes of Health provided financial support (NS26150 to P.C.B.)
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Supplementary information
Supplementary Fig. 1
Slow outgrowth on PLO is converted to faster outgrowth by blebbistatin treatment. (JPG 73 kb)
Supplementary Fig. 2
Myosin IIC is present in growth cones, and myosin IIB is asymmetrically distributed in growth cones at borders. (JPG 440 kb)
Supplementary Table 1
Relationship between outgrowth rates on different substrates and turning frequencies. (PDF 35 kb)
Supplementary Video 1
Time-lapse of control neurites at laminin-1 borders. A control culture growing on PLO+LN1 (red overlay) shows turning at the border with PLO. (MOV 2507 kb)
Supplementary Video 2
Time-lapse of blebbistatin-treated control neurites at laminin-1 borders. Turning is rare in a blebbistatin treated control culture. (MOV 2837 kb)
Supplementary Video 3
Time-lapse of myosin IIB knockout neurites at laminin-1 borders. A myosin IIB knockout culture shows intermediate behavior; only some neurites turn at the border. (MOV 2642 kb)
Supplementary Video 4
Time-lapse of a myosin IIB knockout neuron transfected with GFP–myosin IIB at a laminin-1 border. A myosin IIB knockout neuron that was transfected with GFP-myosin IIB is shown. The neurite crosses the border, turns and then grows along the border on the side with LN1. Note the periodic extensions toward the border. A small vestigial branch persists at the original border contact site. The substrate is covered with gold particles from biolistics. (MOV 2608 kb)
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Turney, S., Bridgman, P. Laminin stimulates and guides axonal outgrowth via growth cone myosin II activity. Nat Neurosci 8, 717–719 (2005). https://doi.org/10.1038/nn1466
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DOI: https://doi.org/10.1038/nn1466
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