Lissencephaly is a severe brain developmental disease characterized by the mislocalization of cortical neurons, a smooth cerebral surface, mental retardation, and seizures. Classical lissencephaly is caused by sporadic mutations in the LIS1 gene. While LIS1 is known to act in a pathway deactivating the lipid messenger platelet-activating factor, LIS1 forms a complex with Nudel and 14-3-3e which is then transported from neuronal cell bodies through the actions of DISC1 and KIF5A, a microtubule-dependent directed motor protein kinesin. Decreased expression of LIS1 blocked neural stem cell division, morphogenesis, and motility, suggesting that LIS1 plays an important role in neuronal cell proliferation and localization in the developing brain. At least two isoforms of LIS1 are known to exist.
Wnt Signaling Pathway
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