QBI, University of Queensland, Australia
Thursday 18 December 2008
Seminar Room B10 (Basement)
Alexandra House, 17 Queen Square, London, WC1N 3AR
Measuring and modeling the limits of axon guidance by molecular gradients
Growth cone guidance by molecular gradients plays a crucial role in wiring up the nervous system. A quantitative understanding of the molecular computations growth cones use to detect gradients is a crucial requirement for being able to manipulate axon guidance during development and in axonal regeneration after injury. In this talk, I will review two critical steps we have taken towards such an understanding. I provide the first complete quantitative mapping of the degree to which axons respond to gradients as receptor binding statistics are systematically varied, showing reliably measurable responses to concentation differences as low as 1/100th of a single molecule across the growth cone. Such an impressive performance suggests that axons may be operating near fundamental physical limits to detection. Therefore, I present the results of a Bayesian "ideal observer" analysis, based on the hypothesis that the principal constraint on gradient detection is intrinsic receptor binding noise. This analysis accurately reproduces the form of the guidance response. Together these results reveal the quantitative constraints that must be satisfied for effective axonal guidance, and the computational principles that may be employed by the underlying signal transduction pathways.