The cellular roles of the lissencephaly gene LIS1, and what they tell us about brain development

摘要

Lissencephaly is a severe brain developmental disease characterized by mislocalization of cortical neurons. This class of diseases has received considerable recent attention for their promise in shedding light on the mechanisms underlying the massive waves of neural progenitor cell migration required for brain development. Classical lissencephaly results from sporadic mutations in the human LIS1 gene, which has been implicated in regulating the microtubule motor protein cyto-plasmic dynein. This connection supports a role for LIS1 in cell motility, and suggests that defects in dynein-mediated movement are responsible for lissencephaly. This article reviews evidence regarding the cellular defects contributing to classical lissencephaly, with emphasis on recent live analysis of LIS1-deficient neural progenitor cell motility in brain tissue