title: LIS1 functions in normal development and disease.
abstract: LIS1, the first gene to be identified as involved in a neuronal migration disease, is a dosage-sensitive gene whose proper levels are required for multiple aspects of cortical development. Deletions in LIS1 result in a severe brain malformation, known as lissencephaly, whereas duplications delay brain development. LIS1 affects the proliferation of progenitors, spindle orientation and interkinetic nuclear movement in the ventricular zone, as well as nucleokinesis and migration of neurons. LIS1 regulatory interaction with the minus end directed molecular motor cytoplasmic dynein is the key for understanding its complex cellular functions. LIS1-dynein interaction decreases the average velocity of the molecular motor in vitro, shows more complex effects in vivo, and may be of importance in high-load transport especially in neurons.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: orly.reiner@weizmann.ac.il.
authors: Orly
authors: O
authors: Reiner
authors: Tamar
authors: T
authors: Sapir
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D054082:Lissencephaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C513190:Pafah1b1 protein, mouse; D004398:Dyneins