Mortimer, D and Feldner, J and Vaughan, T and Vetter, I and Pujic, Z and Rosoff, WJ and Burrage, K and Dayan, P and Richards, LJ and Goodhill, GJ (2009) A Bayesian model predicts the response of axons to molecular gradients. P NATL ACAD SCI USA , 106 (25) 10296 - 10301. 10.1073/pnas.0900715106.
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Axon guidance by molecular gradients plays a crucial role in wiring up the nervous system. However, the mechanisms axons use to detect gradients are largely unknown. We first develop a Bayesian "ideal observer'' analysis of gradient detection by axons, based on the hypothesis that a principal constraint on gradient detection is intrinsic receptor binding noise. Second, from this model, we derive an equation predicting how the degree of response of an axon to a gradient should vary with gradient steepness and absolute concentration. Third, we confirm this prediction quantitatively by performing the first systematic experimental analysis of how axonal response varies with both these quantities. These experiments demonstrate a degree of sensitivity much higher than previously reported for any chemotacting system. Together, these results reveal both the quantitative constraints that must be satisfied for effective axonal guidance and the computational principles that may be used by the underlying signal transduction pathways, and allow predictions for the degree of response of axons to gradients in a wide variety of in vivo and in vitro settings.
|Title:||A Bayesian model predicts the response of axons to molecular gradients|
|Keywords:||axon guidance, chemotaxis, growth cone, nerve growth factor, nerve regeneration, NERVE GROWTH-FACTOR, CHEMOTACTIC RESPONSE, GUIDANCE, MECHANISMS, RECEPTOR, INFORMATION, SYSTEM, CELLS, CONES, CHEMOATTRACTANT|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Gatsby Computational Neuroscience Unit|
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