title: Lissencephaly: mechanistic insights from animal models and potential therapeutic strategies.
abstract: Lissencephaly is a severe human neuronal migration defect characterized by a smooth cerebral surface, mental retardation and seizures. The two most common genes mutated in patients with lissencephaly are LIS1 and DCX. LIS1 was the first gene cloned that was important for neuronal migration in any organism, and heterozygous mutations or deletions of LIS1 are found in the majority of patients with lissencephaly, while DCX mutations were found in males with X-linked lissencephaly. In this review, we will discuss how an understanding of the molecular and cellular pathways disrupted in model organisms with Lis1 and Dcx mutations or knock-down not only provide insights into the normal processes of neuronal migration, including neurogenesis, but they also may lead to potential novel therapeutic strategies for these severe cortical malformations.
authors.affiliation: UCSF School of Medicine, Department of Pediatrics, San Francisco, CA 94143, USA. wynshawborist@peds.ucsf.edu
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: Tiziano
authors.initials: T
authors.lastname: Pramparo
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Youn
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000818:Animals; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D054082:Lissencephaly / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats
chemical_list: C000714328:DCX protein, human; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human