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Axonal branching allows a neuron to connect to several targets, increasing neuronal circuit complexity. While axonal branching is well described, the mechanisms that control it remain largely unknown. We find that in the Drosophila CNS branches develop through a process of excessive growth followed by pruning. In vivo high-resolution live imaging of developing brains as well as loss and gain of function experiments show that activation of Epidermal Growth Factor Receptor (EGFR) is necessary for branch dynamics and the final branching pattern. Live imaging also reveals that intrinsic asymmetry in EGFR localization regulates the balance between dynamic and static filopodia. Elimination of signaling asymmetry by either loss or gain of EGFR function results in reduced dynamics leading to excessive branch formation. In summary, we propose that the dynamic process of axon branch development is mediated by differential local distribution of signaling receptors. DOI: http://dx.doi.org/10.7554/eLife.01699.001, eLife digest In the human brain, 100 billion neurons form 100 trillion connections. Each neuron consists of a cell body with numerous small branch-like projections known as dendrites (from the Greek word for ‘tree’), plus a long cable-like structure called the axon. Neurons receive electrical inputs from neighboring cells via their dendrites, and then relay these signals onto other cells in their network via their axons. The development of the brain relies on new neurons integrating successfully into existing networks. Axon branching helps with this by enabling a single neuron to establish connections with several cells, but it is unclear how individual neurons decide when and where to form branches. Now, Zschätzsch et al. have revealed the mechanism behind this process in the fruit fly, Drosophila. Mutant flies that lack a protein called EGFR produce abnormal numbers of axon branches, suggesting that this molecule regulates branch formation. Indeed in fruit flies, just as in mammals, the developing brain initially produces excessive numbers of branches, which are subsequently pruned to leave only those that have formed appropriate connections. In Drosophila, an uneven distribution of EGFR between branches belonging to the same axon acts as a signal to regulate this pruning process. To examine this mechanism in more detail, high-resolution four-dimensional imaging was used to study brains that had been removed from Drosophila pupae and kept alive in special culture chambers. Axon branching and loss could now be followed in real time, and were found to occur more slowly in brains that lacked EGFR. The receptor controlled the branching of axons by influencing the distribution of another protein called actin, which is a key component of the internal skeleton that gives cells their structure. In addition to providing new insights into a fundamental aspect of brain development, the work of Zschätzsch et al. also highlights the importance of stochastic events in shaping the network of connections within the developing brain. These findings may well be relevant to ongoing efforts to map the human brain ‘connectome’. DOI: http://dx.doi.org/10.7554/eLife.01699.002