Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling.
Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling.
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DOI：
10.1038/ncomms15157
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发表时间：
2017-05-02
影响因子：
16.6
通讯作者：
Hashimoto-Torii K
中科院分区：
文献类型：
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作者：
Ishii S;Torii M;Son AI;Rajendraprasad M;Morozov YM;Kawasawa YI;Salzberg AC;Fujimoto M;Brennand K;Nakai A;Mezger V;Gage FH;Rakic P;Hashimoto-Torii K
重复产前暴露于相同或相似剂量的有害物质会对胎儿大脑发育产生高度可变和不可预测的负面影响，严重程度从高到低或无。然而，这种变异性的分子和细胞基础还没有得到很好的理解。这项研究报告说，小鼠和人类胚胎脑组织暴露于相同剂量的有害化学物质，如乙醇，激活主要的应激反应转录因子热休克因子1（Hsf 1）在一个高度可变和随机的方式。虽然Hsf 1对于保护胚胎大脑免受环境压力至关重要，但过度激活会损害关键的发育事件，如神经元迁移。我们的研究结果表明，镶嵌激活Hsf 1在胚胎大脑中的产前环境压力暴露可能有助于产生复杂的先天性脑疾病中观察到的表型变异。众所周知，产前暴露于环境压力会损害皮质发育。在这里，作者表明，在暴露于应激源时，Hsf 1-Hsp信号的激活在小鼠胚胎皮层的细胞中是高度可变的，激活过多或过少都可能导致皮层发育缺陷。
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. Prenatal exposure to environmental stressors is known to impair cortical development. Here the authors show that upon exposure to stressors, the activation of Hsf1-Hsp signalling is highly variable among cells in the embryonic cortex of mice, and either too much or too little activation can result in defects in cortical development.