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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