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

Jin Wu Tsai, Yu Chen, Arnold R. Kriegstein, Richard B. Vallee*

*此作品的通信作者

研究成果: Article同行評審

346 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)935-945
頁數11
期刊Journal of Cell Biology
170
發行號6
DOIs
出版狀態Published - 12 9月 2005

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