Genetics of neuronal migration in the cerebral cortex.

The development of the cerebral cortex requires large-scale movement of neurons from areas of proliferation to areas of differentiation and adult function in the cortex proper, and the patterns of this neuronal migration are surprisingly complex. The migration of neurons is affected by several naturally occurring genetic defects in humans and mice; identification of the genes responsible for some of these conditions has recently yielded new insights into the mechanisms that regulate migration. Other key genes have been identified via the creation of induced mutations that can also cause dramatic disorders of neuronal migration. However, our understanding of the physiological and biochemical links between these genes is still relatively spotty. 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 genes 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 migration. MRDD Research Reviews 6:34-40, 2000. Copyright 2000 Wiley-Liss, Inc.