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First published online 21 September 2005
doi: 10.1242/dev.02029

Development 132, 4545-4552 (2005)
Published by The Company of Biologists 2005
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Adaptation is not required to explain the long-term response of axons to molecular gradients

Jun Xu1, William J. Rosoff1, Jeffrey S. Urbach2 and Geoffrey J. Goodhill3,*

1 Department of Neuroscience, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20007, USA
2 Department of Physics, Georgetown University, 37th and O Streets NW, Washington, DC 20057, USA
3 Queensland Brain Institute, Department of Mathematics and Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia

* Author for correspondence (e-mail: g.goodhill{at}uq.edu.au)

Accepted 5 August 2005

It has been suggested that growth cones navigating through the developing nervous system might display adaptation, so that their response to gradient signals is conserved over wide variations in ligand concentration. Recently however, a new chemotaxis assay that allows the effect of gradient parameters on axonal trajectories to be finely varied has revealed a decline in gradient sensitivity on either side of an optimal concentration. We show that this behavior can be quantitatively reproduced with a computational model of axonal chemotaxis that does not employ explicit adaptation. Two crucial components of this model required to reproduce the observed sensitivity are spatial and temporal averaging. These can be interpreted as corresponding, respectively, to the spatial spread of signaling effects downstream from receptor binding, and to the finite time over which these signaling effects decay. For spatial averaging, the model predicts that an effective range of roughly one-third of the extent of the growth cone is optimal for detecting small gradient signals. For temporal decay, a timescale of about 3 minutes is required for the model to reproduce the experimentally observed sensitivity.

Key words: Axon guidance, Chemotaxis, Computational model, Nerve growth factor, Dorsal root ganglion




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A. C. von Philipsborn, S. Lang, J. Loeschinger, A. Bernard, C. David, D. Lehnert, F. Bonhoeffer, and M. Bastmeyer
Growth cone navigation in substrate-bound ephrin gradients
Development, July 1, 2006; 133(13): 2487 - 2495.
[Abstract] [Full Text] [PDF]


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