对Xenopus自组织信号通路的分子分析,从蛋到尾茎的轴向模式
Yagmur Azbazdar1, Edward M De Robertis1
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662.
概括
鸟胚胎的发育依赖于顺序信号传递. 关键发现揭示了Chordin和Nodal可以诱导β-catenin耗尽胚胎的完整轴,独立于β-catenin活动,突出显示新的发育途径.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 胚胎发生是胚胎发生.
背景情况:
- 背腹 (D-V) 和前后 (A-P) 轴形成对于胚胎发育至关重要.
- 了解控制Xenopus胚胎细胞分化的顺序信号通路是必不可少的.
研究的目的:
- 在Xenopus胚胎中剖析控制D-V和AP细胞分化的信号通路.
- 研究特定信号分子和对手在轴形成中的作用.
主要方法:
- 在Xenopus胚胎中使用了功能丧失和功能获取方法.
- 微注射特定的mRNA和蛋白质 (Hwa,β-catenin,节点相关因子,BMP4,Dkk1).
- 使用β-catenin激活Luciferase记者和表型救援实验分析信号通路活动.
主要成果:
- 华蛋白激活早期β-catenin信号,诱导双胞胎轴.
- 与Xenopus节点相关的因素拯救β-catenin耗尽,并被Cerberus-Short和Lefty抑制.
- BMP抗体Chordin和Noggin在没有β-catenin的胚胎中拯救D-V和AP组织,令人惊的是没有β-catenin的转录活性.
- 迪克科夫 (Dkk1) 通过抑制晚期Wnt信号与Hwa协同作用;它的效果由Sizzled (Szl) 调节.
- BMP4抑制了Hwa诱导的轴,而Dkk1则抑制了晚期的BMP信号传递.
结论:
- 胚胎轴形成涉及复杂的,上下文依赖的信号相互作用.
- 在特定条件下,Chordin和Nodal可以独立于β-catenin转录活性来诱导完整的胚胎轴.
- 迪克科普f1的前部化和背部化作用是由晚期BMP信号调节的介导,需要Sizzled.
- 化诱导的脊柱化依赖于节点.
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