Engineered cell culture substrates for axon guidance studies: moving beyond proof of concept

Promoting axon regeneration following injury is one of the ultimate challenges of neuroscience, and understanding the mechanisms that regulate axon growth and guidance is essential to achieve this goal. During development axons are directed over relatively long distances by a precise extracellular distribution of chemical signals in the embryonic nervous system. Multiple guidance proteins, including netrins, slits, semaphorins, ephrins and neurotrophins have been identified as key players in this process. During the last decade, engineered cell culture substrates have been developed to investigate the cellular and molecular mechanisms underlying axon guidance. This review is focused on the biological insights that have been achieved using new techniques that attempt to mimic in vitro the spatial patterns of proteins that growth cones encounter in vivo.