Radial unit hypothesis of neocortical expansion.

The more than 1000-fold increase in the cortical surface without a comparable increase in its thickness during mammalian evolution can be explained in the context of the radial unit hypothesis of cortical development. Cortical expansion results from changes in the proliferation kinetics of founder cells in the ventricular zone that increase the number of radial columnar units without significantly changing the number of neurons within each unit. Thus, regulatory genes that control the timing (onset/rate/duration) and mode (symmetrical/asymmetrical) of cell divisions and the magnitude of programmed cell death (apoptosis) in the ventricular zone determine the number of cortical cells in a given species. The migration of postmitotic cells and their allocation into appropriate positions within the cortex is radially constrained by glial scaffolding and thereby creates an expanded cortical plate in the form of a sheet. Several families of genes and morphoregulatory molecules that control the production, migration and deployment of neurons within the developing cortical plate are being identified and their functions tested in vitro and in transgenic animals. The results provide a hint of how mutation of genes that regulate the early stages of corticogenesis may determine the species-specific size and basic organization of the cerebral cortex that sets the stage for the formation of the final pattern of its synaptic connections that can be validated through natural selection.