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LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages
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 a...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171430/ https://www.ncbi.nlm.nih.gov/pubmed/16144905 http://dx.doi.org/10.1083/jcb.200505166 |
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author | Tsai, Jin-Wu Chen, Yu Kriegstein, Arnold R. Vallee, Richard B. |
author_facet | Tsai, Jin-Wu Chen, Yu Kriegstein, Arnold R. Vallee, Richard B. |
author_sort | Tsai, Jin-Wu |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2171430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21714302008-03-05 LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages Tsai, Jin-Wu Chen, Yu Kriegstein, Arnold R. Vallee, Richard B. J Cell Biol Research Articles 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. The Rockefeller University Press 2005-09-12 /pmc/articles/PMC2171430/ /pubmed/16144905 http://dx.doi.org/10.1083/jcb.200505166 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Tsai, Jin-Wu Chen, Yu Kriegstein, Arnold R. Vallee, Richard B. LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
title | LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
title_full | LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
title_fullStr | LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
title_full_unstemmed | LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
title_short | LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
title_sort | lis1 rna interference blocks neural stem cell division, morphogenesis, and motility at multiple stages |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171430/ https://www.ncbi.nlm.nih.gov/pubmed/16144905 http://dx.doi.org/10.1083/jcb.200505166 |
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