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Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition

Author

Listed:
  • Alysson R. Muotri

    (The Salk Institute for Biological Studies)

  • Vi T. Chu

    (The Salk Institute for Biological Studies
    Chemicon International, Inc.)

  • 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)

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.

Suggested Citation

  • Alysson R. Muotri & Vi T. Chu & Maria C. N. Marchetto & Wei Deng & John V. Moran & Fred H. Gage, 2005. "Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition," Nature, Nature, vol. 435(7044), pages 903-910, June.
    • Handle: RePEc:nat:nature:v:435:y:2005:i:7044:d:10.1038_nature03663
    DOI: 10.1038/nature03663
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    Cited by:

    1. Bert I. Crawford & Mary Jo Talley & Joshua Russman & James Riddle & Sabrina Torres & Troy Williams & Michelle S. Longworth, 2024. "Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Damiano Mangoni & Alessandro Simi & Pierre Lau & Alexandros Armaos & Federico Ansaloni & Azzurra Codino & Devid Damiani & Lavinia Floreani & Valerio Carlo & Diego Vozzi & Francesca Persichetti & Claud, 2023. "LINE-1 regulates cortical development by acting as long non-coding RNAs," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Chen Sun & Kunal Kathuria & Sarah B. Emery & ByungJun Kim & Ian E. Burbulis & Joo Heon Shin & Daniel R. Weinberger & John V. Moran & Jeffrey M. Kidd & Ryan E. Mills & Michael J. McConnell, 2024. "Mapping recurrent mosaic copy number variation in human neurons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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