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

First Author  Ishii S Year  2017
Journal  Nat Commun Volume  8
Pages  15157 PubMed ID  28462912
Mgi Jnum  J:249555 Mgi Id  MGI:5921431
Doi  10.1038/ncomms15157 Citation  Ishii S, et al. (2017) Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling. Nat Commun 8:15157
abstractText  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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