title: Cytoskeleton in action: lissencephaly, a neuronal migration disorder.
abstract: During neocortical development, the extensive migratory movements of neurons from their place of birth to their final location are essential for the coordinated wiring of synaptic circuits and proper neurological function. Failure or delay in neuronal migration causes severe abnormalities in cortical layering, which consequently results in human lissencephaly ('smooth brain'), a neuronal migration disorder. The brains of lissencephaly patients have less-convoluted gyri in the cerebral cortex with impaired cortical lamination of neurons. Since microtubule (MT) and actin-associated proteins play important functions in regulating the dynamics of MT and actin cytoskeletons during neuronal migration, genetic mutations or deletions of crucial genes involved in cytoskeletal processes lead to lissencephaly in human and neuronal migration defects in mouse. During neuronal migration, MT organization and transport are controlled by platelet-activating factor acetylhydrolase isoform 1b regulatory subunit 1 (PAFAH1B1, formerly known as LIS1, Lissencephaly-1), doublecortin (DCX), YWHAE, and tubulin. Actin stress fibers are modulated by PAFAH1B1 (LIS1), DCX, RELN, and VLDLR (very low-density lipoprotein receptor)/LRP8 (low-density lipoprotein-related receptor 8, formerly known as APOER2). There are several important levels of crosstalk between these two cytoskeletal systems to establish accurate cortical patterning in development. The recent understanding of the protein networks that govern neuronal migration by regulating cytoskeletal dynamics, from human and mouse genetics as well as molecular and cellular analyses, provides new insights on neuronal migration disorders and may help us devise novel therapeutic strategies for such brain malformations.
authors.forename: Hyang Mi
authors.initials: HM
authors.lastname: Moon
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
mesh_terms: D000818:Animals; D002465:Cell Movement; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000089662:Doublecortin Protein; D006801:Humans; D054082:Lissencephaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054081:Malformations of Cortical Development, Group II / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D000091042:Reelin Protein
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse