Human brain malformations and their lessons for neuronal migration

The developmental steps required to build a brain have been recognized as a distinctive sequence since the turn of the twentieth century. As marking t ools for experimental embryology emerged, the cellular events of cortical h istogenesis have been intensively scrutinized. On this rich backdrop, molec ular genetics provides the opportunity to play out the molecular programs t hat orchestrate these cellular events. Genetic studies of human brain malfo rmation have proven a surprising source for finding the molecules that regu late CNS neuronal migration. These studies also serve to relate the signifi cance of genes first identified in murine species to the more complex human brain. The known genetic repertoire that is special to neuronal migration in brain has rapidly expanded over the past five years, making this an appr opriate time to take stock of the emerging picture. We do this from the per spective of human brain malformation syndromes, noting both what is now kno wn of their genetic bases and what remains to be discovered.