LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages

• DOI: 10.1083/jcb.200505166
• Publication Date: 2005-09-07T00:34:12Z
• Authors: Jin-Wu Tsai; Yu Chen; Arnold R. Kriegstein; Richard B. Vallee
• Keywords: Neuroepithelial cell

Mutations in the human LIS1 gene cause smooth brain disease classical lissencephaly. To understand underlying mechanisms, we conducted situ live cell imaging analysis of function throughout entire radial migration pathway. In utero electroporation small interference RNA and short hairpin dominant negative dynactin cDNAs caused a dramatic accumulation multipolar progenitor cells within subventricular zone embryonic rat brains. This effect resulted from complete failure progression to migratory bipolar state, as revealed by time-lapse slices. Surprisingly, interkinetic nuclear oscillations glial progenitors were also abolished, divisions at ventricular surface. Those few that reached intermediate exhibited block somal translocation, although, remarkably, process extension persisted. Finally, axonal growth ceased. These results identify multiple distinct novel roles for nucleokinesis dynamics suggest position controls neural division.