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.

1. Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
2. Department of Human Genetics and Internal Medicine, 1241 E. Catherine Street, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA
3. †Present address: Department of Cell Biology, Chemicon International, Inc., 28820 Single Oak Drive, Temecula, California 92590, USA
4. *These authors contributed equally to this work

Correspondence to: Fred H. Gage¹ Correspondence and requests for materials should be addressed to F.H.G. (Email: gage@salk.edu).
Microarray data have been deposited in the GEO archive under accession number GSE2499, and the Cl22 L1 insertion sequence has been deposited in GenBank under accession number AY995186.

Received 7 March 2005; Accepted 20 April 2005

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