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

Authors: Tsai, JW  Chen, Y  Kriegstein, AR  Vallee, RB 
Citation: Tsai JW, etal., J Cell Biol. 2005 Sep 12;170(6):935-45. Epub 2005 Sep 6.
Pubmed: (View Article at PubMed) PMID:16144905
DOI: Full-text: DOI:10.1083/jcb.200505166

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.

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RGD Object Information
RGD ID: 1601501
Created: 2007-04-23
Species: All species
Last Modified: 2007-04-23
Status: ACTIVE



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