Molecular mechanisms of neuronal migration disorders, quo vadis?
Following terminal mitosis, neuronal precursor cells leave their site of origin and migrate towards their definitive site of residency. In order to establish the intricate cytoarchitecture described in the adult human brain, neuronal migration must be finely regulated. In humans, brain malformations can result from neuronal migration defects. The spectrum of migration disorder severity extends from few heterotopic neurons, as observed in periventricular heterotopia, to a complete cortical disorganization, as observed in cases of lissencephaly. Recently, specific migration disorders have been linked to mutations/deletions in the doublecortin, filamin-1, LIS1 and reelin genes. These proteins act at different levels of the signaling cascades transducing extracellular guiding cues into cytoskeletal reorganization. Here, we summarize the data concerning these four molecules and speculate on their functions and interaction partners during neuronal development.
Couillard-Despres
S
S
Volkswagen Foundation Junior Group, University of Regensburg, Germany.
Winkler
J
J
Uyanik
G
G
Aigner
L
L
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002455:Cell Division; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002540:Cerebral Cortex / Q000196:embryology; D003285:Contractile Proteins / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins / Q000235:genetics; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction
D015816:Cell Adhesion Molecules, Neuronal; D003285:Contractile Proteins; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins; D064448:Filamins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C000717127:RELN protein, human; D012697:Serine Endopeptidases