title: Molecular genetics of neuronal migration disorders.
abstract: Cortical malformations associated with defects in neuronal migration result in severe developmental consequences including intractable epilepsy and intellectual disability. Genetic causes of migration defects have been identified with the advent and widespread use of high-resolution MRI and genetic techniques. Thus, the full phenotypic range of these genetic disorders is becoming apparent. Genes that cause lissencephaly, pachygyria, subcortical band heterotopia, and periventricular nodular heterotopias have been defined. Many of these genes are involved in cytoskeletal regulation including the function of microtubules (LIS1, TUBA1A,TUBB3, and DCX) and of actin (FilaminA). Thus, the molecular pathways regulating neuronal migration including the cytoskeletal pathways appear to be defined by human mutation syndromes. Basic science, including cell biology and animal models of these disorders, has informed our understanding of the pathogenesis of neuronal migration disorders and further progress depends on the continued integration of the clinical and basic sciences.
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, 111 Michigan Avenue, NW, Suite M7642, Washington, DC, USA. jliu@cnmcresearch.org
authors.forename: Judy S
authors.initials: JS
authors.lastname: Liu
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D003285:Contractile Proteins / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D016326:Extracellular Matrix Proteins / Q000235:genetics; D064448:Filamins; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D054081:Malformations of Cortical Development, Group II / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008870:Microtubules / Q000378:metabolism; D008967:Molecular Biology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: C119088:ARFGEF2 protein, human; C469264:ARX protein, human; D015816:Cell Adhesion Molecules, Neuronal; D003285:Contractile Proteins; C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D016326:Extracellular Matrix Proteins; D064448:Filamins; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011973:Receptors, LDL; D000091042:Reelin Protein; D014157:Transcription Factors; D014404:Tubulin; C036053:VLDL receptor; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D012697:Serine Endopeptidases