TY - JOUR
T1 - Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling
AU - Ishii, Seiji
AU - Torii, Masaaki
AU - Son, Alexander I.
AU - Rajendraprasad, Meenu
AU - Morozov, Yury M.
AU - Kawasawa, Yuka Imamura
AU - Salzberg, Anna C.
AU - Fujimoto, Mitsuaki
AU - Brennand, Kristen
AU - Nakai, Akira
AU - Mezger, Valerie
AU - Gage, Fred H.
AU - Rakic, Pasko
AU - Hashimoto-Torii, Kazue
N1 - 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 Jérôme 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 Jérôme 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.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms15157
DO - 10.1038/ncomms15157
M3 - Article
C2 - 28462912
AN - SCOPUS:85019703503
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
M1 - 15157
ER -