右手信号通路驱动脊椎动物的心脏循环
Oscar H Ocaña1, Hakan Coskun1, Carolina Minguillón2
1Instituto de Neurociencias (CSIC-UMH), Avenida Ramón y Cajal, s/n, Sant Joan d'Alacant, Alicante, Spain.
Nature
|September 8, 2017
概括
一项新的研究揭示了骨形态蛋白 (BMP) 信号如何在斑马鱼胚胎中建立右侧不对称性. 这种途径激活Prrx1a,驱动正确的心脏发育和左右身体模式所必需的分离细胞运动.
科学领域:
- 发育生物学
- 胚胎学
- 分子生物学
背景情况:
- 脊椎动物表现出对器官功能至关重要的内部左右不对称性,但确立右侧身份的机制仍然不清楚.
- 已知左侧特定的Nodal-Pitx2路径,但对平行右侧指导路径的理解较少.
- 大多数动物的外侧对称性掩盖了对发育至关重要的复杂的内部不对称性.
研究的目的:
- 研究脊椎动物胚胎发育中左右不对称的分子机制.
- 在胚胎形成过程中提供右手特定信息的途径.
- 阐明Prrx1a在心脏循环和L/R模式中的作用.
主要方法:
- 使用斑马鱼作为模型生物来研究L/R不对称性.
- 研究了骨形态蛋白 (BMP) 在激活Prrx1a中的作用.
- 使用基因操纵 (Prrx1a的下调) 和观察到对心脏发育的影响.
- 在和小鼠胚胎中检查了保存机制.
主要成果:
- 证明BMP信号不对称地激活Prrx1a在侧板中皮层中,右侧的水平更高.
- 显示Prrx1a诱导细胞向中线的差异移动,通过依赖于actomyosin的机制导致心脏向左移动.
- 发现Prrx1a下调导致心脏循环缺陷并导致中心.
- 确定了对心脏形态发生的Pitx2和Prrx1转录因子的并行,相互抑制的节点和BMP通路.
结论:
- 左右表皮介质过渡 (EMT) 产生不对称的细胞运动和力量,主要来自右侧,驱动脊椎动物的心脏侧向.
- 这项研究揭示了一种涉及BMP-Prrx1a和Nodal-Pitx2通道的保存机制,用于确定心脏发育的L/R不对称性.
- 这项工作为控制脊椎动物胚胎器官位置和功能的基本过程提供了新的见解.
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