Can Molecular Gradients Wire the Brain?

Concentration gradients are believed to play a key role in guiding axons to their appropriate targets during neural development. However, there are fundamental physical constraints on gradient detection, and these strongly limit the fidelity with which axons can respond to gradient cues. I discuss these constraints and argue they suggest that many axon guidance events in vivo cannot be explained solely in terms of gradient-based mechanisms. Rather, precise wiring requires the collaboration of gradients with other types of guidance cues. Since we know relatively little about how this might work, I argue that our understanding of how the brain becomes wired up during development is still at an early stage.