Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling
Year: 2017
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms15157
Institutions: Children's National, George Washington University, Yale University, Pennsylvania State University, Yamaguchi University, Salk Institute for Biological Studies, Icahn School of Medicine at Mount Sinai, Centre National de la Recherche Scientifique, Epigénétique et Destin Cellulaire, Université Paris Diderot, NeuroDiderot
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Yale University, Children's National Hospital, Agence Nationale de la Recherche, National Institutes of Health, Japan Society for the Promotion of Science, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Analysis of environmental stress response downstream cascade in cerebral cortex formation, THE IMPACT OF FETAL STRESS ON MENTAL HEALTH : Heat Shock Factors (HSF) as mediators of epigenetic events., District of Columbia Intellectual and Developmental Disabilities Research Center, The roles of alcohol-inducible RNA-operons in the fetal brain, Mechanisms leading to cortical dysplasia in Fetal Alcohol Spectrum Disorders, G5729742867, Regulation of the heat shock response by mitochondrial signals, Transcriptional regulation and DNA repair mechanism of HSF1-PARP complex by DNA damage stimulation, Origin of Cortical Species-specific Distinctions
OpenAlex ID: W2611050861