Reelin and apolipoprotein E receptor 2 in the embryonic and mature brain: effects of an evolutionary change in the apoER2 gene.

In the mature cerebral cortex of higher vertebrates, neurons are arranged in layers, each layer containing neurons of the same functional class. The cortical layering pattern is laid down during development by migration of young post-mitotic neurons along glial fibres to their correct positions in the cortical plate. The mechanics of whole-cell movement are well understood, but there is still uncertainty as to how a migrating neuron is instructed to leave its glial support when it reaches its destination. An intraneuronal signalling pathway initiated by reelin and containing apolipoprotein E receptor 2 (apoER2) is essential for normal cortical layering, and there is strong evidence that detachment of a migrating neuron is brought about by reelin-dependent downregulation of alpha3 integrin. But there remains the problem of how the reelin signal is switched on at a position in the cortex appropriate for each class of neuron. ApoER2 of placental mammals contains an amino acid sequence that is encoded in a separate exon in the apoER2 gene and is required for normal memory and spatial learning. The separate exon is not present in marsupials, birds or reptiles. The addition of this exon to the evolving apoER2 gene may have contributed to the success of placental mammals.