原生素通过调节哺乳动物胚胎中的GDF11/SMAD2信号来促进从干到尾的HOX代码过渡
Yu-Sheng Hung1, Wei-Mi Lin1,2, Yu-Chiuan Wang3
1Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan (ROC).
Communications biology
|December 20, 2024
概括
原生素 (Prtg) 通过调节霍克斯基因表达,对脊椎轴向模式至关重要. 通过GDF11/SMAD2通路,Prtg损失会破坏这一过程,影响胚胎发育.
科学领域:
- 发育生物学是发展生物学.
- 遗传学 是一个遗传学.
- 分子信号传递是分子信号传递.
背景情况:
- 脊椎轴向模式对于胚胎发育至关重要.
- 多个信号网络调节了这个复杂的过程.
- 免疫球蛋白超级家族成员,如原原蛋白 (Prtg) 的作用尚未完全理解.
研究的目的:
- 阐明原生素 (Prtg) 在脊椎轴向模式中的功能.
- 研究Prtg在胚胎发生过程中影响基因表达的分子机制.
- 确定Prtg在转化生长因子β (TGFβ) 信号通路中的作用.
主要方法:
- 产生和分析Prtg淘汰赛 (Prtg-/-) 的小鼠.
- 对Prtg-/-小鼠胚胎进行转录组分析.
- 对化Smad2 (pSmad2) 水平和下游目标的分析.
- 同免疫沉以评估Prtg-GDF11的相互作用.
- 实验使用人类诱导的多能干细胞衍生前体性半皮样细胞 (hiPSC-PSM) 细胞.
主要成果:
- Prtg-/-小鼠表现出前部同源转换和改变的homeobox (Hox) 基因表达.
- 转录基因分析显示,Prtg调节轴向发育基因,特别是在TGFβ通路内.
- 在Prtg-/-胚胎中观察到降低的TGFβ信号传递 (降低的psmad2).
- Prtg 与生长分化因子11 (GDF11) 相互作用,以增强GDF11/pSmad2信号传递.
- 在hiPSC-PSM细胞中,PRTG淘汰会延迟后部HOX基因表达,而后部HOX基因表达则被GDF11.11所拯救.
结论:
- PRTG是脊椎轴向模式和霍克斯基因表达的关键调节者.
- 通过调节GDF11/SMAD2信号通路来实现PRTG的功能.
- 这些发现揭示了控制胚胎轴向发育的新型机制.
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