A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish
A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish
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DOI：
10.1242/dev.060046
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发表时间：
2011-04-01
期刊：
影响因子：
4.6
通讯作者：
Woo, Stephanie
中科院分区：
文献类型：
--
作者：
Fish, Jason E.;Wythe, Joshua D.;Woo, Stephanie
Sit家族成员的分泌配体与环状(Robo)受体相互作用，为许多细胞类型提供指导信号。例如，Sit/Robo信号在神经发育过程中引起轴突的排斥，而在内皮细胞中，这一途径根据细胞环境抑制或促进血管生成。在这里，我们证明了miR-218是在SLIT2和SLIT3中内含子编码的，并且它抑制了Robo1和Robo2的表达。我们的数据表明，miR-218和多个Sit/Robo信号元件是斑马鱼心管形成所必需的，这个网络调节了先前未被认识的VEGF信号在这一过程中的功能。这些发现为基于microRNA的配体-受体相互作用的控制提供了一个新的范例，并为调节脊椎动物心管组装的新的信号通路提供了证据。
Members of the Slit family of secreted ligands interact with Roundabout ( Robo) receptors to provide guidance cues for many cell types. For example, Slit/Robo signaling elicits repulsion of axons during neural development, whereas in endothelial cells this pathway inhibits or promotes angiogenesis depending on the cellular context. Here, we show that miR-218 is intronically encoded in slit2 and slit3 and that it suppresses Robo1 and Robo2 expression. Our data indicate that miR-218 and multiple Slit/Robo signaling components are required for heart tube formation in zebrafish and that this network modulates the previously unappreciated function of Vegf signaling in this process. These findings suggest a new paradigm for microRNA-based control of ligand-receptor interactions and provide evidence for a novel signaling pathway regulating vertebrate heart tube assembly.