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Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition

Alysson R. Muotri, Vi T. Chu, Maria C. N. Marchetto, Wei Deng, John V. Moran and Fred H. Gage ()
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Alysson R. Muotri: The Salk Institute for Biological Studies
Vi T. Chu: The Salk Institute for Biological Studies
Maria C. N. Marchetto: The Salk Institute for Biological Studies
Wei Deng: The Salk Institute for Biological Studies
John V. Moran: University of Michigan Medical School
Fred H. Gage: The Salk Institute for Biological Studies

Nature, 2005, vol. 435, issue 7044, 903-910

Abstract: Abstract Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human LINE-1 (for long interspersed nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fate in vitro. We further show that retrotransposition of a human L1 in transgenic mice results in neuronal somatic mosaicism. The molecular mechanism of action is probably mediated through Sox2, because a decrease in Sox2 expression during the early stages of neuronal differentiation is correlated with increases in both L1 transcription and retrotransposition. Our data therefore indicate that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.

Date: 2005
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DOI: 10.1038/nature03663

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