During nervous system development, axons navigate to their targets by responding to environmental guidance signals and by following pioneer axons. The role of this second mechanism is mainly unexplored in large vertebrate axon tracts, but Pittman and co-workers now demonstrate that interactions between zebrafish retinotectal axons play a key role in guiding axons from the retina to the tectum (see ). To study the role of axon-axon interactions in retinotectal development, the researchers selectively removed early-born retinal ganglion cells (RGCs) by knocking down ath5, a transcription factor needed for the development of these cells. Early-born RGCs, they report, are both necessary and sufficient for later axons to exit the eye. Further experiments in which transplanted axons that lack the Robo2 guidance receptor replaced the early-born RGCs indicate that axon guidance from eye to tectum also relies heavily on axon-axon interactions. Overall, the researchers conclude that axon-axon interactions and environmental guidance signals have equal and cooperative roles in axon guidance in developing vertebrate axon tracts.
