LIS1: cellular function of a disease-causing gene

Brain development is severely defective in children with lissencephaly. The highly organized distribution of neurons within the cerebral cortex is dis rupted, a condition that might arise from improper migration of neuronal pr ogenitors to their cortical destinations. Type I lissencephaly results from mutations in the LIS1 gene, which has been implicated in the cytoplasmic d ynein and platelet-activating factor pathways. Recent studies have identifi ed roles for the product of LIS1 in nuclear migration, mitotic spindle orie ntation and chromosome alignment, where it appears to act in concert with c ytoplasmic dynein. A unifying hypothesis for the subcellular function of LI S1 is presented.