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

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, Fred H. Gage, Pasko Rakic, Kazue Hashimoto-Torii

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Article number15157
JournalNature communications
Volume8
DOIs
StatePublished - 2017

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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