Abstract
Coordinated motor behaviors rely on a maze-like network of axonal connections between motoneurons and the body musculature. Since the time of the Renaissance, scientists have been fascinated by the question of how such complex, yet stereotypic, connectivity arises during embryogenesis. Here, we review the long journey of motor axons, which traverse diverse territories along predetermined routes riddled with a wealth of divergent pathway options. We conclude that motor axon migration occurs in a stepwise manner, with each step being controlled by local guidance cues, that motor axons rely on some of the same cues that also control axon migration within the CNS, and that, due to species-specific anatomical variations, the cell types providing such local cues may vary. Although studies of motor axon migration have not yet resulted in a complete understanding of the cellular and molecular mechanisms regulating this process, we have come a long way since the days of da Vinci.
