Format

Send to

Choose Destination
Nat Commun. 2017 May 2;8:15157. doi: 10.1038/ncomms15157.

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

Author information

1
Center for Neuroscience Research, Children's National Medical Center, Washington, District of Columbia 20010, USA.
2
Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
3
Department of Pediatrics, Pharmacology and Physiology, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia 20052, USA.
4
Department of Biomedical Engineering, School of Engineering and Applied Science, George Washington University, Washington, District of Columbia 20052, USA.
5
Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, Pennsylvania 17033, USA.
6
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, Pennsylvania 17033, USA.
7
Institute for Personalized Medicine, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, Pennsylvania 17033, USA.
8
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube 755-8505, Japan.
9
Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
10
Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA.
11
CNRS, UMR7216 Epigenetics and Cell Fate, Paris 75205, France.
12
University Paris Diderot, 75205 Paris, France.
13
Département Hospitalo-Universitaire DHU PROTECT, Paris 75019, France.

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.

PMID:
28462912
PMCID:
PMC5418582
DOI:
10.1038/ncomms15157
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center