The corpus callosum (CC) is the major interhemispheric fibre bundle in the eutherian brain and has been described as a true evolutionary innovation. This paper reviews the current literature with regard to functional, developmental and genetic concepts that may help elucidate the evolutionary origin of this structure. It has been suggested that the CC arose in the eutherian brain as a more direct and, therefore, more effective system for the interhemispheric integration of topographically organized sensory cortices than the anterior commissure (AC) and hippocampal commissure (HC) already present in nonplacental mammals. It can also be argued, however, that the ability of the CC to integrate the newly evolving motor cortices of placental mammals may have played a role in the evolutionary fixation of this structure. Investigations into the developmental mechanism involved in the formation of the CC and their underlying patterns of gene expression make it possible to formulate a tentative hypothesis about the evolutionary origin of this commissure. This paper suggests that changes in the developmental patterns of the expression of certain regulatory genes may have allowed a first group of callosal pioneering axons to cross the cortical midline. These pioneering fibres may have used the axons of the HC to find their way across the midline. Additional callosal fibres may then have fasciculated with these pioneers. Once the CC had formed in this way, more complex systems of axonal guidance may have evolved over time, thus enabling a gradual increase in the size and complexity of the CC.

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