LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. Tsai, J., Chen, Y., Kriegstein, A. R, & Vallee, R. B J Cell Biol, 170(6):935–945, September, 2005.
abstract   bibtex   
Mutations in the human LIS1 gene cause the smooth brain disease classical lissencephaly. To understand the underlying mechanisms, we conducted in situ live cell imaging analysis of LIS1 function throughout the entire radial migration pathway. In utero electroporation of LIS1 small interference RNA and short hairpin dominant negative LIS1 and dynactin cDNAs caused a dramatic accumulation of multipolar progenitor cells within the subventricular zone of embryonic rat brains. This effect resulted from a complete failure in progression from the multipolar to the migratory bipolar state, as revealed by time-lapse analysis of brain slices. Surprisingly, interkinetic nuclear oscillations in the radial glial progenitors were also abolished, as were cell divisions at the ventricular surface. Those few bipolar cells that reached the intermediate zone also exhibited a complete block in somal translocation, although, remarkably, process extension persisted. Finally, axonal growth also ceased. These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics and suggest that nuclear position controls neural progenitor cell division.
@ARTICLE{Tsai2005-ei,
  title    = "{LIS1} {RNA} interference blocks neural stem cell division,
              morphogenesis, and motility at multiple stages",
  author   = "Tsai, Jin-Wu and Chen, Yu and Kriegstein, Arnold R and Vallee,
              Richard B",
  abstract = "Mutations in the human LIS1 gene cause the smooth brain disease
              classical lissencephaly. To understand the underlying mechanisms,
              we conducted in situ live cell imaging analysis of LIS1 function
              throughout the entire radial migration pathway. In utero
              electroporation of LIS1 small interference RNA and short hairpin
              dominant negative LIS1 and dynactin cDNAs caused a dramatic
              accumulation of multipolar progenitor cells within the
              subventricular zone of embryonic rat brains. This effect resulted
              from a complete failure in progression from the multipolar to the
              migratory bipolar state, as revealed by time-lapse analysis of
              brain slices. Surprisingly, interkinetic nuclear oscillations in
              the radial glial progenitors were also abolished, as were cell
              divisions at the ventricular surface. Those few bipolar cells
              that reached the intermediate zone also exhibited a complete
              block in somal translocation, although, remarkably, process
              extension persisted. Finally, axonal growth also ceased. These
              results identify multiple distinct and novel roles for LIS1 in
              nucleokinesis and process dynamics and suggest that nuclear
              position controls neural progenitor cell division.",
  journal  = "J Cell Biol",
  volume   =  170,
  number   =  6,
  pages    = "935--945",
  month    =  sep,
  year     =  2005,
  language = "en"
}

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