Protein-protein interactions, cytoskeletal regulation and neuronal migration

Neuronal migration, like the migration of many cell types, requires an exte nsive rearrangement of cell shape, mediated by changes in the cytoskeleton. The genetic analysis of human brain malformations has identified several b iochemical players in this process, including doublecortin (DCX) and LIS1, mutations of which cause a profound migratory disturbance known as lissence phaly ('smooth brain') in humans. Studies in mice have identified additiona l molecules such as Cdk5, P35, Reelin, Disabled and members of the LDL supe rfamily of receptors. Understanding the cell biology of these molecules has been a challenge, and it is not known whether they function in related bio chemical pathways or in very distinct processes. The last year has seen rap id advances in the biochemical analysis of several such molecules. This ana lysis has revealed roles for some of these molecules in cytoskeletal regula tion and has shown an unexpected conservation of the genetic pathways that regulate neuronal migration in humans and nuclear movement in simple eukary otic organisms.