Pathogenesis of migration disorders.

PURPOSE OF REVIEW

Neocortical neurons have to migrate from their site of production in the periventricular germinative zone or in the ganglionic eminence towards the cortical plate. Our understanding of the underlying molecular mechanisms has advanced considerably in recent years due to the identification of genes involved in human migration disorders and experimental studies. This review will highlight some of the most recent findings in the deciphering of the molecular machinery controlling neuronal migration.

RECENT FINDINGS

Neuronal migration is a complex process which involves cytoskeletal molecules controlling the initiation of migration, leading edge extension and nucleokinesis; signalling molecules (the reelin pathway playing a central role) integrating external signals and linking them to the cytoskeleton; stop signals; and other molecular players including neurotrophins, glutamate receptors and peroxisome-derived factors. Emerging evidence supports the existence of cross-talk between these pathways.

SUMMARY

Identifying these mechanisms has shed light on typical human neuronal migration disorders such as periventricular heterotopias (disorder of migration initiation linked to filamin), type I lissencephaly (cytoskeletal abnormality linked to Lis1, a microtubule-associated protein), double cortex syndrome (cytoskeletal abnormality linked to doublecortin, a microtubule-associated protein), or lissencephaly plus cerebellar hypoplasia (reelin defect).