Max von Kleist

The idea of guidance toward a target is central to axon pathfinding and brain wiring in general. In this work, we show how several thousand axonal growth cones self-pattern without target-dependent guidance during neural superposition wiring in Drosophila . Ablation of all target lamina neurons or loss of target adhesion prevents the stabilization but not the development of the pattern. Intravital imaging at the spatiotemporal resolution of growth cone dynamics in intact pupae and data-driven dynamics simulations reveal a mechanism by which >30,000 filopodia do not explore potential targets, but instead simultaneously generate and navigate a dynamic filopodial meshwork that steers growth directions. Hence, a guidance mechanism can emerge from the interactions of the axons being guided, suggesting self-organization as a more general feature of brain wiring.