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Among the best-known facts of the brain are the contralateral visual,auditory, sensational, and motor mappings in the forebrain. How and why didthese evolve? The few theories to this question provide functional answers,such as better networks for visuomotor control. However, these theoriescontradict the data, as discussed here. Instead we propose that a 90-degleft-turn around the body-axis evolved in a common ancestor of all vertebrates.Compensatory migrations of the tissues during development restore bodysymmetry. Eyes, nostrils and forebrain compensate in the direction of the turn,whereas more caudal structures migrate in the opposite direction. As a resultof these opposite migrations the forebrain becomes crossed and inverted withrespect to the rest of the nervous system. We show that these compensatorymigratory movements can indeed be observed in the zebrafish (Danio rerio) andthe chick (Gallus gallus). With a model we show how the axial twist hypothesispredicts that an optic chiasm should develop on the ventral side of the brain,whereas the olfactory tract should be uncrossed. In addition, the hypothesisexplains the decussation of the trochlear nerve, why olfaction is non-crossed,why the cerebellar hemispheres represent the ipsilateral bodyside, why insharks the forebrain halves each represent the ipsilateral eye, why the heartand other inner organs are asymmetric in the body. Due to the poor fossilrecord, the possible evolutionary scenarios remain speculative. Molecularevidence does support the hypothesis. The findings may throw new insight on theproblematic structure of the forebrain.

An ancestral axial twist explains the contralateral forebrain and the optic chiasm in vertebrates