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Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster

Author

Listed:
  • Bert I. Crawford

    (Lerner Research Institute, Cleveland Clinic)

  • Mary Jo Talley

    (Lerner Research Institute, Cleveland Clinic)

  • Joshua Russman

    (Lerner Research Institute, Cleveland Clinic)

  • James Riddle

    (Lerner Research Institute, Cleveland Clinic)

  • Sabrina Torres

    (Lerner Research Institute, Cleveland Clinic)

  • Troy Williams

    (Lerner Research Institute, Cleveland Clinic)

  • Michelle S. Longworth

    (Lerner Research Institute, Cleveland Clinic
    Case Western Reserve University School of Medicine)

Abstract

Neural stem and progenitor cell (NSPC) maintenance is essential for ensuring that organisms are born with proper brain volumes and head sizes. Microcephaly is a disorder in which babies are born with significantly smaller head sizes and cortical volumes. Mutations in subunits of the DNA organizing complex condensin have been identified in microcephaly patients. However, the molecular mechanisms by which condensin insufficiency causes microcephaly remain elusive. We previously identified conserved roles for condensins in repression of retrotransposable elements (RTEs). Here, we show that condensin subunit knockdown in NSPCs of the Drosophila larval central brain increases RTE expression and mobility which causes cell death, and significantly decreases adult head sizes and brain volumes. These findings suggest that unrestricted RTE expression and activity may lead to improper brain development in condensin insufficient organisms, and lay the foundation for future exploration of causative roles for RTEs in other microcephaly models.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47042-9
    DOI: 10.1038/s41467-024-47042-9
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    References listed on IDEAS

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    1. Omer Ali Bayraktar & Chris Q. Doe, 2013. "Combinatorial temporal patterning in progenitors expands neural diversity," Nature, Nature, vol. 498(7455), pages 449-455, June.
    2. James H. Notwell & Tisha Chung & Whitney Heavner & Gill Bejerano, 2015. "A family of transposable elements co-opted into developmental enhancers in the mouse neocortex," Nature Communications, Nature, vol. 6(1), pages 1-7, May.
    3. Marco Cecco & Takahiro Ito & Anna P. Petrashen & Amy E. Elias & Nicholas J. Skvir & Steven W. Criscione & Alberto Caligiana & Greta Brocculi & Emily M. Adney & Jef D. Boeke & Oanh Le & Christian Beaus, 2019. "L1 drives IFN in senescent cells and promotes age-associated inflammation," Nature, Nature, vol. 566(7742), pages 73-78, February.
    4. Hale Tunbak & Rocio Enriquez-Gasca & Christopher H. C. Tie & Poppy A. Gould & Petra Mlcochova & Ravindra K. Gupta & Liane Fernandes & James Holt & Annemarthe G. Veen & Evangelos Giampazolias & Kathlee, 2020. "The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    5. J. Kenneth Baillie & Mark W. Barnett & Kyle R. Upton & Daniel J. Gerhardt & Todd A. Richmond & Fioravante De Sapio & Paul M. Brennan & Patrizia Rizzu & Sarah Smith & Mark Fell & Richard T. Talbot & St, 2011. "Somatic retrotransposition alters the genetic landscape of the human brain," Nature, Nature, vol. 479(7374), pages 534-537, November.
    6. 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.
    7. Andreas Holleufer & Kasper Grønbjerg Winther & Hans Henrik Gad & Xianlong Ai & Yuqiang Chen & Lihua Li & Ziming Wei & Huimin Deng & Jiyong Liu & Ninna Ahlmann Frederiksen & Bine Simonsen & Line Lykke , 2021. "Two cGAS-like receptors induce antiviral immunity in Drosophila," Nature, Nature, vol. 597(7874), pages 114-118, September.
    8. Yoshinori Kawamura & Kuniaki Saito & Taishin Kin & Yukiteru Ono & Kiyoshi Asai & Takafumi Sunohara & Tomoko N. Okada & Mikiko C. Siomi & Haruhiko Siomi, 2008. "Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells," Nature, Nature, vol. 453(7196), pages 793-797, June.
    9. Alysson R. Muotri & Maria C. N. Marchetto & Nicole G. Coufal & Ruth Oefner & Gene Yeo & Kinichi Nakashima & Fred H. Gage, 2010. "L1 retrotransposition in neurons is modulated by MeCP2," Nature, Nature, vol. 468(7322), pages 443-446, November.
    10. Marco Cecco & Takahiro Ito & Anna P. Petrashen & Amy E. Elias & Nicholas J. Skvir & Steven W. Criscione & Alberto Caligiana & Greta Brocculi & Emily M. Adney & Jef D. Boeke & Oanh Le & Christian Beaus, 2019. "Author Correction: L1 drives IFN in senescent cells and promotes age-associated inflammation," Nature, Nature, vol. 572(7767), pages 5-5, August.
    11. Benjamin Czech & Colin D. Malone & Rui Zhou & Alexander Stark & Catherine Schlingeheyde & Monica Dus & Norbert Perrimon & Manolis Kellis & James A. Wohlschlegel & Ravi Sachidanandam & Gregory J. Hanno, 2008. "An endogenous small interfering RNA pathway in Drosophila," Nature, Nature, vol. 453(7196), pages 798-802, June.
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