The great crossing: Three centuries of inquiry into why the vertebrate nervous system decussates

Decussation, the crossing of axonal fiber bundles from one side of the neuraxis to the other, is among the most conspicuous and least explained principles of vertebrate nervous system organization. This review follows the problem historically rather than thematically. It opens with what the anatomy investigators were attempting to account for, then traces the argument as it developed: from the Hippocratic observation of crossed paralysis and the chiasmos of Aretaeus, through the demonstrations of Mistichelli and Pourfour du Petit and the nineteenth-century mapping of the sensory tracts and the partial optic chiasm, to the answer Ramón y Cajal gave in 1898 and its erosion thereafter. The accounts offered in its place include comparative arguments from the distribution of crossing among vertebrates, topological and wiring-economy models, the escape-circuit tradition of the Mauthner cell, and the revival of an 1822 proposal about dorsoventral inversion in the twist hypotheses. The molecular biology of midline guidance and recent computational work are read as continuations of that argument rather than departures from it. Decussation emerges not as one phenomenon with one cause but as a family of crossings of heterogeneous origin, some adaptive and some incidental to an ancestral change in body plan.