A quantitative analysis of branching, growth cone turning, and directed growth in zebrafish retinotectal axon guidance



The topographic projection from the eye to the tectum (amphibians and fish)/superior colliculus (birds and mammals) is a paradigm model system for studying mechanisms of neural wiring development. It has previously been proposed that retinal ganglion cell axons use distinct guidance strategies in fish vs. mammals, with direct guidance to the tectal target zone in the former and overshoot followed by biased branching toward the target zone in the latter. Here we visualized individual retinal ganglion cell axons as they grew over the tectum in zebrafish for periods of 10-21 hours and analyzed these results using an array of quantitative measures. We found that, although axons were generally guided directly toward their targets, this occurred without growth cone turning. Instead, axons branched dynamically and profusely throughout pathfinding, and successive branches oriented growth cone extension toward a target zone in a stepwise manner. These data suggest that the guidance strategies used between fish and mammals may be less distinct than previously thought. J. Comp. Neurol., 521:1409–1429, 2013. © 2012 Wiley Periodicals, Inc.