Elevated and sustained reactive oxygen species levels facilitate mesoderm formation during early Xenopus development
Elevated and sustained reactive oxygen species levels facilitate mesoderm formation during early Xenopus development
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DOI：
10.1101/223453
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发表时间：
2017-11
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影响因子：
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通讯作者：
Yue Han;Yaoyao Chen;Nick R. Love;Shoko Ishibashi;E. Amaya
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文献类型：
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作者：
Yue Han;Yaoyao Chen;Nick R. Love;Shoko Ishibashi;E. Amaya
受精触发胚胎发育，最终激活一些高度协调和进化保守的信号通路，诱导和模式发育中的胚胎的中胚层。之前对无脊椎动物的研究表明，过氧化氢（H2O2）是一种活性氧（ROS），可以在早期发育过程中作为轴规范的信号分子。我们最近发现，通过对母系表达h2o2敏感荧光蛋白传感器的超转基因非洲爪蟾株系，受精触发ROS产生的快速增加。在这里，我们发现这种ROS水平的增加持续整个早期胚胎发生，一直持续到尾芽阶段。此外，我们表明，通过抗氧化处理降低从囊胚期到原胚期的ROS水平会破坏中胚层的形成。此外，我们发现在囊胚/原胚阶段降低ROS水平会影响一些（但不是全部）参与中胚层诱导和模式的生长因子信号通路，包括PI3K/Akt、TGF-β/Nodal和Wnt/β-catenin信号通路。这些数据表明，在囊胚和原胚阶段持续升高的ROS水平对早期脊椎动物胚胎发育至关重要，至少部分是通过它们在促进生长因子信号传导中的作用。
Fertilisation triggers embryonic development culminating with the activation of a number of highly co-ordinated and evolutionarily conserved signalling pathways, which induce and pattern the mesoderm of the developing embryo. Previous studies in invertebrates have shown that hydrogen peroxide (H2O2), a reactive oxygen species (ROS), can act as a signalling molecule for axis specification during early development. Using a HyPer transgenic Xenopus laevis line that expresses a H2O2-sensitive fluorescent protein sensor maternally, we recently found that fertilisation triggers a rapid increase in ROS production. Here we show that this increase in ROS levels is sustained throughout early embryogenesis, lasting until the tailbud stages. In addition we show that lowering ROS levels from the blastula stage through the gastrula stages via antioxidant treatments disrupts mesoderm formation. Furthermore, we show that attenuating ROS levels during the blastula / gastrula stages affects some, but not all, growth factor signalling pathways involved in mesoderm induction and patterning, including the PI3K/Akt, TGF-β/Nodal, and Wnt/β-catenin signalling pathways. These data suggest that sustained elevated ROS levels during the blastula and gastrula stages are essential for early vertebrate embryonic development, at least partly, through their roles in promoting growth factor signalling.