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Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling

Author

Listed:
  • Seiji Ishii

    (Center for Neuroscience Research, Children's National Medical Center)

  • Masaaki Torii

    (Center for Neuroscience Research, Children's National Medical Center
    Yale University School of Medicine
    Pharmacology and Physiology, School of Medicine and Health Sciences, George Washington University)

  • Alexander I. Son

    (Center for Neuroscience Research, Children's National Medical Center)

  • Meenu Rajendraprasad

    (Center for Neuroscience Research, Children's National Medical Center
    School of Engineering and Applied Science, George Washington University)

  • Yury M. Morozov

    (Yale University School of Medicine)

  • Yuka Imamura Kawasawa

    (Pennsylvania State University College of Medicine
    Pennsylvania State University College of Medicine
    Institute for Personalized Medicine, Pennsylvania State University College of Medicine)

  • Anna C. Salzberg

    (Institute for Personalized Medicine, Pennsylvania State University College of Medicine)

  • Mitsuaki Fujimoto

    (Yamaguchi University School of Medicine)

  • Kristen Brennand

    (Icahn School of Medicine at Mount Sinai
    Salk Institute for Biological Studies, Laboratory of Genetics)

  • Akira Nakai

    (Yamaguchi University School of Medicine)

  • Valerie Mezger

    (CNRS, UMR7216 Epigenetics and Cell Fate
    University Paris Diderot
    Département Hospitalo-Universitaire DHU PROTECT)

  • Fred H. Gage

    (Salk Institute for Biological Studies, Laboratory of Genetics)

  • Pasko Rakic

    (Yale University School of Medicine)

  • Kazue Hashimoto-Torii

    (Center for Neuroscience Research, Children's National Medical Center
    Yale University School of Medicine
    Pharmacology and Physiology, School of Medicine and Health Sciences, George Washington University)

Abstract

Repetitive prenatal exposure to identical or similar doses of harmful agents results in highly variable and unpredictable negative effects on fetal brain development ranging in severity from high to little or none. However, the molecular and cellular basis of this variability is not well understood. This study reports that exposure of mouse and human embryonic brain tissues to equal doses of harmful chemicals, such as ethanol, activates the primary stress response transcription factor heat shock factor 1 (Hsf1) in a highly variable and stochastic manner. While Hsf1 is essential for protecting the embryonic brain from environmental stress, excessive activation impairs critical developmental events such as neuronal migration. Our results suggest that mosaic activation of Hsf1 within the embryonic brain in response to prenatal environmental stress exposure may contribute to the resulting generation of phenotypic variations observed in complex congenital brain disorders.

Suggested Citation

  • Seiji Ishii & Masaaki Torii & Alexander I. Son & Meenu Rajendraprasad & Yury M. Morozov & Yuka Imamura Kawasawa & Anna C. Salzberg & Mitsuaki Fujimoto & Kristen Brennand & Akira Nakai & Valerie Mezger, 2017. "Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15157
    DOI: 10.1038/ncomms15157
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