Pathogenesis of migration disorders.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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).
INSERM U676, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France. gressens@debre.inserm.fr
Pierre
P
Gressens
D000818:Animals; D001119:Arginase; D001927:Brain Diseases / Q000145:classification / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003042:Cocaine / Q000009:adverse effects; D003599:Cytoskeleton / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D019579:Neocortex / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D020675:Peroxisomes; D000091042:Reelin Protein; D015398:Signal Transduction / Q000502:physiology
D000091042:Reelin Protein; C000717127:RELN protein, human; D001119:Arginase; D003042:Cocaine