NOTCH maintains developmental cardiac gene network through WNT5A.
NOTCH maintains developmental cardiac gene network through WNT5A.
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NOTCH 通过 WNT5A 维持发育心脏基因网络。
DOI：
10.1016/j.yjmcc.2018.10.014
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发表时间：
2018
影响因子：
5
通讯作者：
Zhou,Bin
中科院分区：
文献类型：
--
作者：
Wang,Yidong;Lu,Pengfei;Wu,Bingruo;Morrow,BerniceE;Zhou,Bin
NOTCH和WNT信号通路在心腔形成中起关键作用。在这里，我们探讨了这两个途径之间的潜在相互作用，在这个发展过程中，通过使用转基因小鼠模型和全胚胎培养系统。通过在体内和离体挽救实验中删除Notch 1到Notch NOTCH 1信号，我们表明心肌WNT 5A介导的Notch 1信号维持了心腔形成所必需的基因调控网络。此外，心肌中β-连环蛋白的基因缺失和FK 506对WNT/Ca 2+信号传导的抑制导致基因调控网络的破坏与内源性N 0 TCH 1信号传导的失活相似。这些发现确定WNT 5A是一个关键的心肌因子，它介导内皮细胞NOTCH信号，通过WNT/β-连环蛋白和WNT/Ca 2+维持心腔形成所必需的基因调控网络信号通路
NOTCH and WNT signaling pathways play critical roles in cardiac chamber formation. Here we explored the potential interactions between the two pathways in this developmental process by using genetically modified mouse models and whole embryo culture systems. By deletion ofNotch1to inactivate NOTCH1 signaling in the endocardium in vivo and ex vivo rescue experiments, we showed that myocardial WNT5A mediated endocardial NOTCH1 signaling to maintain the gene regulatory network essential for cardiac chamber formation. Furthermore, genetic deletion of β-catenin in the myocardium and inhibition of the WNT/Ca2+signaling by FK506 resulted in a similar disruption of the gene regulatory network as inactivation of endocardial NOTCH1 signaling.Together, these findings identify WNT5A as a key myocardial factor that mediates the endocardial NOTCH signaling to maintain the gene regulatory network essential for cardiac chamber formation through WNT/β-catenin and WNT/Ca2+signaling pathways.