Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition

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. Vive la difference seems fair comment when it comes to the organization of the vertebrate brain and mind. The basic kit of parts can achieve considerable variation between individuals. A source of variability in the neuronal genome that might explain some of the differences is reported this week: retrotransposition by LINE-1 regulatory elements. In adult rat neuronal stem cells, and in vivo in brains of transgenic mice, an engineered human LINE-1 is shown to produce DNA from RNA by reverse transcription. Similar retrotranspositions have been seen previously in germ cells or in early embryogenesis, before the cells had adopted a distinct (neuronal, say) lineage. But this new work suggests that mobile genetic elements might alter the neuronal genome — and neuronal circuits — at a much later stage.