Genetics of neuronal migration in the cerebral cortex

The development of the cerebral cortex requires large-scale movement of neu rons from areas of proliferation to areas of differentiation and adult func tion in the cortex proper, and the patterns of this neuronal migration are surprisingly complex. The migration of neurons is affected by several natur ally occurring genetic defects in humans and mice; identification of the ge nes responsible for some of these conditions has recently yielded new insig hts into the mechanisms that regulate migration. Other key genes have been identified via the creation of induced mutations that can also cause dramat ic disorders of neuronal migration. However, our understanding of the physi ological and biochemical links between these genes is still relatively spor ty. A number of molecules have also been studied in mice (Reelin, mDab1,and the VLDL and ApoE2 receptors) that appear to represent part of a coherent signaling pathway that regulates migration, because multiple genes cause an indistinguishable phenotype when mutated. On the other hand, two human gen es that cause lissencephaly (LIS1, DCX) encode proteins that have recently been implicated as regulators or microtubule dynamics. This article reviews some of the mutant phenotypes in light of the mechanisms of neuronal migra tion. (C) 2000 Wiley-Liss, Inc.