Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition

Bibliographic Collection: 
CARTA-Inspired Publication, APE
Publication Type: Journal Article
Authors: Muotri, A. R.; Chu, V. T.; Marchetto, M. C.; Deng, W.; Moran, J. V.; Gage, F. H.
Year of Publication: 2005
Journal: Nature
Volume: 435
Edition: 2005/06/17
Number: 7044
Pagination: 903-10
Date Published: Jun 16
Type of Article: Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.
Publication Language: eng
ISBN Number: 1476-4687 (Electronic)00
Accession Number: 15959507
Keywords: Animals, Brain/cytology/metabolism, Cell Differentiation, Cell Lineage, Cells, Cultured, DNA-Binding Proteins/genetics, Gene Expression Regulation, Green Fluorescent Proteins/genetics/metabolism, HMGB Proteins/genetics, Humans, Long Interspersed Nucleotid

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.


EnglandNature. 2005 Jun 16;435(7044):903-10.

Alternate Journal: Nature
Author Address:

Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.