@article{b8fd711ae32a42e9a628d07583ed6cb0,
title = "Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling",
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.",
author = "Seiji Ishii and Masaaki Torii and Son, {Alexander I.} and Meenu Rajendraprasad and Morozov, {Yury M.} and Kawasawa, {Yuka Imamura} and Salzberg, {Anna C.} and Mitsuaki Fujimoto and Kristen Brennand and Akira Nakai and Valerie Mezger and Gage, {Fred H.} and Pasko Rakic and Kazue Hashimoto-Torii",
note = "Funding Information: We thank Sho Yamada, Miki Masuda, and Hiroki Naito for their technical assistance, and Dr. Aminah Sheikh for critical reading of the manuscript. VM laboratory has been supported by the Agence Nationale pour la Recherche (Program SAMENTA ANR-13-SAMA-0008-01), Fondation J{\'e}r{\^o}me Lejeune, and IREB/FRA (2014/18). This work was supported by a NIH/NIAAA (R00AA01838705, R01AA025215), CTSI-CN Pilot Research Award and Avery Translational Research Career Development Program Award from Children's National Medical Center, Brain and Behavior Research Foundation (Scott-Gentle Foundation and Essel Foundation), ABMRF, and the Kavli Institute for Neuroscience at Yale Funding Information: We thank Sho Yamada, Miki Masuda, and Hiroki Naito for their technical assistance, and Dr. Aminah Sheikh for critical reading of the manuscript. VM laboratory has been supported by the Agence Nationale pour la Recherche (Program SAMENTA ANR-13-SAMA-0008-01), Fondation J{\'e}r{\^o}me Lejeune, and IREB/FRA (2014/18). This work was supported by a NIH/NIAAA (R00AA01838705, R01AA025215), CTSI-CN Pilot Research Award and Avery Translational Research Career Development Program Award from Children{\textquoteright}s National Medical Center, Brain and Behavior Research Foundation (Scott-Gentle Foundation and Essel Foundation), ABMRF, and the Kavli Institute for Neuroscience at Yale. Publisher Copyright: {\textcopyright} The Author(s) 2017.",
year = "2017",
doi = "10.1038/ncomms15157",
language = "English (US)",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}